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UV-nanoimprint lithography (UV-NIL) has been proved to be an efficient method for preparing nanodrug delivery systems. Herein, we used UV-NIL associated with the glancing angle deposition (GLAD) process of electron beam evaporation to prepare Au-coated PLGA nanocylinders loaded with PTX (PTX-PLGA-Au NCs) to enhance anticancer efficacy by the cooperative treatment of photothermal-chemotherapy. PTX-PLGA-Au NCs with different length-to-diameter ratios can be prepared by controlling the concentration of PLGA and regulating the angle of GLAD. Upon 808 nm near-infrared (NIR) irradiation, PTX-PLGA-Au NCs exhibit a stable and repeatable photothermal effect. Besides, hyperthermia generated by the Au layer on the surface of PTX-PLGA-Au NCs under laser irradiation promoted the rapid release of PTX. The in vitro studies demonstrated that PTX-PLGA-Au NCs can achieve the synergistic effect of photothermal-chemotherapy, leading to increased cell cytotoxicity. Therefore, UV-NIL combined with the GLAD process produced a promising nanofabrication method for efficiently developing a multifunctional nanoplatform for cancer treatment. [ABSTRACT FROM AUTHOR]

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy. [ABSTRACT FROM AUTHOR]

The tumor microenvironment responsive multifunctional nanoplatforms with integrated diagnosis and therapy have recently received great attention in anti-cancer treatment. In this study, we developed biocompatible iron oxide-hydroxide-based nanorods (DOX-FPT NRs) for MR imaging and H2S scavenging assisted synergistic photothermal-chemotherapy of colon cancer, which is fabricated by modifying polydopamine (PDA) and transferrin (Tf) on the surface of iron oxide hydroxide (FeOOH) nanorods. The prepared DOX-FPT NRs could precisely target the colon cancer cells through transferrin ligand-receptor-mediated targeting and effectively scavenge endogenous H2S to prohibit the growth of colon cancer. Meanwhile, the considerable drug loading capability and outstanding photothermal conversion efficiency are permitted by the PDA shell modification. In addition, the H2S scavenging assisted photothermal-chemotherapy showed an excellent therapeutic effect on CT26 cells via in vitro cell test. Therefore, the prepared DOX-PFT NRs will be a promising nanoplatform to enhance the therapeutic effect of colon cancer through the treatment strategy of H2S scavenging-assisted synergistic photothermal chemotherapy.

Lacking a precise targeting strategy, castration-resistant prostate cancer (CRPC) is still hard to be treat effectively. Exploring treatment options that can accurately target CPRC is an important issue with urgent need. In this study, a novel nanotechnology-based strategy had been developed for the precise target treatment of CRPC. By combining microwaves and photothermal therapy (PTT), this nanoplatform, cmHSP70-PL-AuNC-DOX, targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects. From nanotechnology, cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy. Doxorubicin (DOX) was selected as the chemotherapeutic agent for cytotoxicity. In terms of the curative scheme, prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70 (HSP70) and its migration to the cell membrane, which was then targeted by HSP70 antibody (cmHSP70) coated on the nanoparticles to achieve accurate drug delivery. The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared (NIR) irradiation. Through the implementation, the targeting, cell killing, and safety of this therapeutical strategy had been verified in vivo and in vitro. This work establishes an accurate, controllable, efficient, non-invasive, and safe treatment platform for targeting CRPC, provides a rational design for CRPC's PTT, and offers new prospects for nanomedicines with great precision. [ABSTRACT FROM AUTHOR]

The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDAAS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermalchemotherapy. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and aggressive, but therapies based on single-targeted nanoparticles frequently address these tumors as a single illness. To achieve more efficient drug transport, it is crucial to develop nanodrug-carrying systems that simultaneously target two or more cancer biomarkers. In addition, combining chemotherapy with near-infrared (NIR) light-mediated thermotherapy allows the thermal ablation of local malignancies via photothermal therapy (PTT), and triggers drug release to improve chemosensitivity. Thus, a novel dual-targeted nano-loading system, DOX@GO-HA-HN-1 (GHHD), was created for synergistic chemotherapy and PTT by the co-modification of carboxylated graphene oxide (GO) with hyaluronic acid (HA) and HN-1 peptide and loading with the anticancer drug doxorubicin (DOX). Targeted delivery using GHHD was shown to be superior to single-targeted nanoparticle delivery. NIR radiation will encourage the absorption of GHHD by tumor cells and cause the site-specific release of DOX in conjunction with the acidic microenvironment of the tumor. In addition, chemo-photothermal combination therapy for cancer treatment was realized by causing cell apoptosis under the irradiation of 808-nm laser. In summary, the application of GHHD to chemotherapy combined with photothermal therapy for OSCC is shown to have important potential as a means of combatting the low accumulation of single chemotherapeutic agents in tumors and drug resistance generated by single therapeutic means, enhancing therapeutic efficacy. • Dual-reactive release of nanoparticles under low pH and near-infrared irradiation. • Superior targeting of oral squamous carcinoma cells by dual-targeted nanoparticle substrates. • Chemo-photothermal synergistic treatment of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Surface PEGylation of nanomedicine is effective for prolonging blood circulation time and facilitating the EPR effect, whereas the hydrophilic stealth surface inhibits effective cellular uptake and hinders active targeting. To address the dilemma, herein, a NIR light-triggered dePEGylation/ligand-presenting strategy based on thermal decomposition of azo bonds is developed, whereby Dox/Pz-IR nanoparticle is self-assembled from thermo-labile azo molecule-linked long PEG chain polymer (Pz-IR), cRGD-conjugated IR783 with short PEG chains (rP-IR) and doxorubicin. The long PEG chains could mask cRGD peptides in the blood circulation, preventing serum degradation and nonspecific interaction with normal cells. Once exposed to NIR laser, the PEG corona is stripped off owing to the rupture of azo bonds through the photothermal effect of IR783, and the masked cRGD peptides are exposed, which remarkably enhances cellular uptake by tumor cells and improves tumor accumulation. Dox/Pz-IR achieves the optimal synergy of photothermal-chemotherapy at mild temperature through progressive tumor accumulation, precisely regulated photothermal effect and NIR-PTT induced pulsated drug release. The strategy of NIR photo-driven dePEGylation/targeting offers a new approach to overcoming the "PEG dilemma", and provides a noval avenue for programmed tumor-targeted drug delivery. A NIR light-triggered dePEGylation/ligand-presenting strategy based on thermal decomposition of azo bonds is developed to address the "PEG dilemma" and enhance synergistic antitumor effect of photothermal-chemotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag2S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg2S@mSiO2-TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg2S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Fabrication of a smart drug delivery system based on hollow Ag2S@mSiO2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy [ABSTRACT FROM AUTHOR]

The design and preparation of multifunctional drug carriers for combined photothermal–chemotherapy of cancer have attracted extensive attention over the past few decades. However, the development of simple-structured stimuli-responsive theranostic agents as both photothermal agents and chemotherapeutic agents remains a big challenge. Herein, a novel double-shelled nanocarrier composed of hollow Ag2S (HAg2S) nanospheres and a mesoporous polydopamine (MPDA) exterior shell was fabricated through a facile process. Notably, HAg2S possesses both fluorescence and photothermal properties. MPDA acts as a drug carrier and photothermal agent. Meanwhile, the cavity structure between HAg2S and MPDA provides more space for drug loading. The nanocarrier presents a high drug loading rate of 23.4%. It exhibits an apparent pH-responsive DOX release property due to the acidic sensitivity of PDA. In addition, the release of DOX is promoted under NIR irradiation, which is attributed to the heating action generated by the photothermal effect of HAg2S and MPDA. The cytotoxicity test shows that the nanocarriers possess good biocompatibility. Compared with single photothermal therapy or chemotherapy, the combined treatment represents a synergistic effect with higher therapeutic efficacy. In addition, the nanocarriers exhibit excellent fluorescence imaging capability and can target HepG2 cells. These simple-structured smart nanocarriers have a great potential for fluorescence-mediated combination cancer therapy. [ABSTRACT FROM AUTHOR]

Nanomedicines have been widely used in colorectal cancer treatment, but their suboptimal targeting and deficient penetration capabilities remain obstacles in the delivery of therapeutics. In this study, inspired by the natural tumor tropism and intestinal invasion of Salmonella , we engineered highly biomimetic nanoparticles (SM-AuNRs) utilizing a Salmonella membrane to coat bacilliform Au nanorods. The engineered SM-AuNRs were able to mimic the germ's morphology and biological surface. SM-AuNRs containing the specific proteins inherited from the Salmonella membrane facilitated specific targeting and internalization into tumor cells. Meanwhile, SM-AuNRs with the rod-shaped morphology effectively traversed mucus barriers and tumor stroma. Due to the superior biological barrier penetrating and tumor targeting capabilities, doxorubicin-loaded SM-AuNRs with near-infrared laser irradiation displayed remarkable photothermal-chemotherapeutic antitumor effects in mouse orthotopic colorectal cancer models. Our findings pave the way for the design of bacteria-mimicking nanoparticles, presenting a promising avenue for the targeting and efficient treatment of colorectal cancer.

A triblock copolymer with mussel-inspired adhesive ability, poly(acryl hydrazide)-b-poly(N-(3, 4- dihydroxyphenylethyl) acrylamide)-b-poly(monomethoxypolyethylene glycol acrylate) (PAH-b-PAD-b-PmPEGA, abbreviated as HDP), was designed and synthesized via reversible addition fragmentation chain transfer polymerization process from three monomers, including 1-tert-butcarbonyl-2-acrylhydrazide(Boc-AH), N-(3, 4-dihydroxyphenylethyl) acrylamide(DA) and poly(ethylene glycol) methyl ether methacrylate (mPEGA). The copolymer was used for decorating gold nanorod (GNR) to obtain GNR-based nanocarrier. Chemotherapeutic drug doxorubicin (DOX) was conjugated onto the nanocarrier by an acid-labile hydrazone linkage, resulting in HDP-GNR-DOX nanodrug. The physicochemical properties of the nanocarrier, such as structure, stability, photothermal performance, and pH-responsive drug release, were characterized. Moreover, the in vitro anti-tumor effect of the nanodrug towards breast cancer cells (MCF-7) was evaluated. Results showed that the DOX content of the nanodrug was as high as 8.1% and the nanodrug exhibited excellent photothermal conversion ability, favorable stability and pH-responsive drug release behavior. Importantly, the results of cellular experiments demonstrated that the nanodrug could be effectively internalized by MCF-7. In the case of near infrared irradiation, the nanodrug showed high apoptosis-inducing ability on MCF-7, achieving highly efficient photothermal-chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Most nanomedicines with suitable sizes (normally 100–200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) −triggered size-shrinkable micelle system (Fe 3 O 4 @AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe 3 O 4 @AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe 3 O 4 @AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe 3 O 4 @Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe 3 O 4 @AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe 3 O 4 @AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration. [ABSTRACT FROM AUTHOR]

Aiming at high drug loading and controlled drug release in chitosan nanocarriers, this work constructed the photothermal sensitive carboxymethyl chitosan nanospheres carrier by introducing controllable heat-sensitive groups into carboxymethyl chitosan molecules. The combination therapy system based on photothermal-chemotherapy was established by virtue of the good photothermal conversion effect of ICG and the high chemotherapy efficiency of DOX. On the one hand, the carrier owned high drug loading and improved the stability of coated-drug. On the other hand, the nanospheres generated photothermal response through NIR irradiation to improve the drug release amount and to achieve the combined treatment effect of photodynamic therapy and chemotherapy. The structures of the nanospheres were fully characterized by Fourier transform infrared (FT-IR), nuclear magnetic resonance (1H NMR) and scanning electron microscope (SEM). In vitro photothermal tests proved that the nanospheres had excellent light stability and photothermal conversion performance. The cytotoxicity test results showed that the nanospheres had no obvious toxicity, but the drug-loaded nanospheres could effectively inhibit the growth of HepG-2 cells via photo-response to release DOX and ICG for achieving photothermal-chemotherapy under NIR irradiation. Unlabelled Image [ABSTRACT FROM AUTHOR]

With the rising threat of cancers, gold nanorods (GNRs) based photothermal–chemotherapy is becoming an increasingly important strategy to cure cancers. There are some challenges faced by GNRs system including complicated synthesis process and low drug loading capacity. In this study, GNRs assisted mesoporous silica nanoparticles (GNR@SiO2 NPs) are fabricated by a simple method. The mesoporous SiO2 can not only prevent the aggregation of GNRs but also provide large hollow mesoporous structure to enhance drug loading capacity. Moreover, GNRs absorb near‐infrared (NIR) light and convert it into heat. The temperature of the GNR@SiO2 solution was increased to ∼60 (2 W) and 90°C (3 W) after NIR radiation. The photothermal conversion efficiency was 32.60% of GNR@SiO2 under NIR light irradiation at 2 W, while 39.01% under NIR light irradiation at 3 W. The drug loading content of GNR@SiO2 was 22.3 ± 2.5%, which was higher than that of most reported GNR drug delivery systems. The authors also found that the GNR@SiO2 @ doxorubicin may have a higher drug release rate under the conditions of the tumour microenvironment. The in vitro cytotoxity of GNR@SiO2 was demonstrated on HeLa cells. The experimental results indicate that GNR@SiO2 has great potential for synergistic treatment to kill cancer cells. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract With great potential in nanomedicine, the integration of a metal organic framework (MOF) with a nanocarrier for smart and versatile cancer theranostics still seeks to expand. In this study, MOF was successfully merged with hollow mesoporous organosilica nanoparticles (HMONs) with a polydopamine (PDA) interlayer to form molecularly organic/inorganic hybridized nanocomposites (HMONs-PMOF). The well-defined nanostructure and favorable biocompatibility of HMONs-PMOF were demonstrated first. Doxorubicin hydrochloride (DOX) and indocyanine green (ICG) were separately loaded into the interior cavity of HMONs and the outer porous shell of MOF with high loading efficacy, respectively. The obtained dual drug-loaded nanocomposites (DI@HMONs-PMOF) displayed favorable photothermal properties and pH/NIR-triggered DOX release manner. Furthermore, in vitro cell experiments validated that HMONs-PMOF can efficiently deliver DOX into cancer cells. Upon entry into cancer cells, the photothermal effect of DI@HMONs-PMOF can induce the lysosome rupture, thereby facilitating the "lysosome escape" process and accelerating the DOX diffusion in the cytoplasm. Benefiting from the iron ion coordinated on PDA and ICG confined in MOF, magnetic resonance (MR) and photoacoustic (PA) dual-modality imaging were performed to verify the effective accumulation of DI@HMONs-PMOF at the tumor site. Interestingly, the results also suggested that the existence of ICG can cooperatively enhance the MR imaging capability of prepared nanocomposites. In addition, the significantly improved synergistic therapeutic efficacy was confirmed both in vitro and in vivo. Thus, our results indicated that the merged nanostructure of HMONs and MOF is promising for versatile cancer theranostics. Statement of Significance Metal organic framework (MOF) has recently emerged as a class of fascinating nanocarriers. The integration of MOF with other nanostructures can endow the new nanoformulation with collective functionality and synergistic performance that are not accessed from single-component nanostructure. Herein, we reported the successful merging of MOF and hollow mesoporous organosilica nanoparticles (HMONs) to form a hollow nanocontainer with a well-defined nanostructure. The large cavity of HMONs and highly porous network of MOF enable high drug loading efficacy. Moreover, the dual-modality magnetic resonance and photoacoustic imaging can be realized, which is also benefited from the merged nanostructure. Overall, we expected this paradigm could pave way for integrating MOF with other nanocarriers to achieve more diverse applications. [ABSTRACT FROM AUTHOR]

Recently, Combined cancer photothermal-chemotherapy has become a highly promising strategy in cancer treatment for its enhanced therapeutic efficacy, controlled drug release and reduced systemic toxicity. Almost all the reported strategies based on photothermal-chemotherapy have only focused on the treatment of superficial or subcutaneous cancer, which are not considered as a more clinically relevant and better predictive models of drug efficacy than orthotopic tumor models. Here, we reported an EphB4 receptor-targeting polymeric nanoplatform containing hollow gold nanospheres (HAuNS) and the anticancer drug paclitaxel (PTX) for cancer photothermal-chemotherapy. With the modification of the TNYL peptide, HP-TCS could specifically internalize into EphB4-positive SKOV3 and CT26 cells, further inducing the selective killing of the cells in co-cultured system, namely, EphB4-positive and EphB4-negative cells. Obvious targeting of the micelles into implanted orthotopic or subcutaneous tumors with high EphB4 expression was observed. Interestingly, increased accumulation of HP-TCS was observed in orthotopic colon tumors when compared with ectopic tumors. Highly specific accumulation of HP-TCS in EphB4-positive tumors significantly increased the feasibility of photothermal-chemotherapy mediated by the near infrared reflection (NIR) laser. Then, a systemic antitumor efficiency study was performed in implanted subcutaneous and visual orthotopic tumor models. Precise NIR laser irradiation could be localized on tumors under the guidance of B-mode ultrasound imaging, causing a rapid photothermal ablation effect limited to the region of tumors. Tumor growth was significantly inhibited by the photothermal-chemotherapy due to the triggered release of PTX. Our study provided a promising strategy of NIR laser-mediated photothermal-chemotherapy based on HP-TCS against the tumors (specially, deep orthotopic tumors) with high EphB4 expression.

Stimuli-responsive nanoparticles are focused to promote the pathological specificity and controlled therapeutic activation in biomedicine, but the multifunctional modulation remains challenging. Herein, size and morphology switchable phototheranostic nanoparticles are developed for photoacoustic (PA) imaging-guided photothermal-chemotherapy. Multifunctional polypyrrole (PPy) nanoparticles with the template of upper critical solution temperature (UCST) polymers are designed to achieve light-controlled pulsatile drug release and concurrent activation of photothermal therapy (PTT). Wherein the UCST-featured inner core is loaded with camptothecin (CPT), the outer corona is tethered with thermo-cleavable doxorubicin (DOX) prodrug and further in-situ coated with PPy, affording the resultant CPT@DOX-UCST/PPy nanoparticles. Upon 808 nm continuous laser illumination, significant heating generated from light-absorbable PPy results in DOX prodrug cleavage and considerable size swelling (∼125-fold), which in turn promotes simultaneous dual drug release, and thus triggering the combined therapeutic activation of PTT and chemotherapy. When laser is switched off, the discontinued photothermal generation makes the nanoparticle shrink back, thereby avoiding the leakage of CPT and DOX. In vivo experiments demonstrate the favorable tumor accumulation and prolonged tumor retention (>24 h) for long-term PA imaging-guided combination therapy. Current multifunctional nanoparticles integrated with light-controlled swelling/shrinking and synergistic therapeutic activation/silence represent a promising platform for precision cancer theranostics. [ABSTRACT FROM AUTHOR]

Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C 16 copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period. Moreover, the specific targeting capability based on CD44 recptor-mediated endocytosis and the enhanced targeting efficacy by in presence of external magnetic field were investigated. The clustered SPIONs within micelles exerted excellent contrast effect with high r 2 relaxivity in MR phantom test. Furthermore, the multifunctional micelles could readily convert light to heat to hyperthermia temperature upon near infrared light irradition and induce photothermal ablation to breast cancer cells. The combined photothermal therapy with DTX-mediated chemotherapy of the developed multifunctional polymeric micells could generate a synergistic therapeutic effect. Based on these findings, the resulting multifunctional micelles may provide high potential for multimodality theragnosis of cancer. [ABSTRACT FROM AUTHOR]

Multifunctional nanoagents have become popular and valuable pharmaceuticals for effective cancer treatment. Moreover, there is an increasing tendency to develop therapeutic agents with excellent biocompatibility, high efficiency, specific targeting and combinatorial treatment effects. In this study, we proposed a facile technique to synthesize PEGylated (polyethylene glycol modified) magnetic Prussian blue (PB) nanoparticles with encapsulated doxorubicin (DOX), abbreviated as Fe 3 O 4 @PB/PEG/DOX NPs, for combined targeted photothermal ablation and pH-triggered chemotherapy of tumour cells. The PEGylation of Fe 3 O 4 @PB core-shell structure was achieved through a thin-film hydration process; DOX was loaded into the nanocapsule via hydrophobic interactions. An in vitro study indicated increased drug release under acidic conditions, mimicking mild acidic tumour microenvironments. Additionally, the nanocomposites exhibited superparamagnetism, contributing to an improved therapeutic effect guided by a localized magnetic field. Cytotoxicity studies demonstrated outstanding photothermal-chemotherapy combinatorial effects on HeLa cells, attributed to the targeted photothermic effect mediated by the pH-triggered cellular uptake of DOX. Specifically, the viability of HeLa cells decreased to 8.5% after treatment with the nanoagent (DOX = 10 μg mL −1 ) and near infrared irradiation, indicating an evident tumour inhibition effect in vitro . This study presented a nanoplatform for efficient and targeted cancer treatment, which may lead to the development of multifunctional nanodrug vehicles for cancer therapy. [ABSTRACT FROM AUTHOR]

Recently, Combined cancer photothermal-chemotherapy has become a highly promising strategy in cancer treatment for its enhanced therapeutic efficacy, controlled drug release and reduced systemic toxicity. Almost all the reported strategies based on photothermal-chemotherapy have only focused on the treatment of superficial or subcutaneous cancer, which are not considered as a more clinically relevant and better predictive models of drug efficacy than orthotopic tumor models. Here, we reported an EphB4 receptor-targeting polymeric nanoplatform containing hollow gold nanospheres (HAuNS) and the anticancer drug paclitaxel (PTX) for cancer photothermal-chemotherapy. With the modification of the TNYL peptide, HP-TCS could specifically internalize into EphB4-positive SKOV3 and CT26 cells, further inducing the selective killing of the cells in co-cultured system, namely, EphB4-positive and EphB4-negative cells. Obvious targeting of the micelles into implanted orthotopic or subcutaneous tumors with high EphB4 expression was observed. Interestingly, increased accumulation of HP-TCS was observed in orthotopic colon tumors when compared with ectopic tumors. Highly specific accumulation of HP-TCS in EphB4-positive tumors significantly increased the feasibility of photothermal-chemotherapy mediated by the near infrared reflection (NIR) laser. Then, a systemic antitumor efficiency study was performed in implanted subcutaneous and visual orthotopic tumor models. Precise NIR laser irradiation could be localized on tumors under the guidance of B-mode ultrasound imaging, causing a rapid photothermal ablation effect limited to the region of tumors. Tumor growth was significantly inhibited by the photothermal-chemotherapy due to the triggered release of PTX. Our study provided a promising strategy of NIR laser-mediated photothermal-chemotherapy based on HP-TCS against the tumors (specially, deep orthotopic tumors) with high EphB4 expression. [ABSTRACT FROM AUTHOR]

Photothermal-chemotherapy (PT-CT) is a promising strategy for cancer treatment, but its development is hindered by the issues regarding to the long-term safety of carriers and imperfect drug release profiles. In this article, we use polyethylene glycol-modified polydopamine nanoparticles (PDA-PEG) as an outstanding PT-CT agent for cancer treatment. PDA-PEG possesses excellent biocompatibility and photothermal effect, and could easily load anticancer drugs such as doxorubicin (DOX) and 7-ethyl-10-hydroxycamptothecin (SN38) via π-π stacking and/or hydrogen binding. Moreover, the drug-loaded PDA-PEG showed great stability and drug-retaining capability in physiological condition, and could respond to multiple stimuli including near infrared light, pH and reactive oxygen species to trigger the release of loaded anticancer drugs. The in vitro and in vivo studies demonstrated that PDA-PEG-mediated PT-CT showed synergetic effect for cancer therapy. [ABSTRACT FROM AUTHOR]

Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer. [ABSTRACT FROM AUTHOR]

Controllable and visible delivery of therapeutic agents is critical for tumor precise therapy. Tumor targeting and deep penetration of therapeutic agents are still challenging issues for controllable delivery. Visible drug delivery with imaging navigation can optimize the treatment window for personalized medicine. Herein, a biomimetic platelet intelligent vehicle with navigation (IRDNP-PLT) was developed to achieve controllable and visible delivery with a navigation system, a driving system, and a loading system. The platelets acted as engines and drug repositories to exert the target driving and delivery functions. The fluorescent photothermal agent IR-820 was introduced in the platform to offer an imaging navigation for the intelligent platelet vehicle in addition to photothermal therapy. The nanodrug-loaded platelets enabled efficient drug loading and controlled release of the therapeutic payload by encapsulating photothermal-/pH-sensitive chemotherapeutic nanoparticles (PDA@Dox NPs). In in vivo experiments on 4T1 tumor-bearing mice models, IRDNP-PLT performed well in tumor targeting and showed excellent therapeutic efficacy and tumor recurrence prevention ability. The intelligent platelet vehicle achieved the functions of tumor targeting and deep penetration, fluorescence imaging guidance, photocontrolled drug release, and chemo-photothermal combination therapy, suggesting the advancement for tumor precise delivery and efficient therapy.

One of the current challenges in the post-operative treatment of breast cancer is to develop a local therapeutic vector for preventing recurrence and metastasis. Herein, we develop a core-shell fibrous scaffold comprising phase-change materials and photothermal/chemotherapy agents, as a thermal trigger for programmable-response drug release and synergistic treatment. The scaffold is obtained by in situ growth of a zeolitic imidazolate framework-8 (ZIF-8) shell on the surface of poly(butylene succinate)/lauric acid (PBS/LA) phase-change fibers (PCFs) to create PCF@ZIF-8. After optimizing the core-shell and phase transition behavior, gold nanorods (GNRs) and doxorubicin hydrochloride (DOX) co-loaded PCF@ZIF-8 scaffolds were shown to significantly enhance in vitro and in vivo anticancer efficacy. In a healthy tissue microenvironment at pH 7.4, the ZIF-8 shell ensures the sustained release of DOX. If the tumor recurs, the acidic microenvironment induces the decomposition of the ZIF-8 shell. Under the second near-infrared (NIR-II) laser treatment, GNR-induced thermal not only directly destroys the relapsed tumor cells but also accelerates DOX release by inducing the phase transition of LA. Our study sheds light on a well-designed programmable-response trigger, which provides a promising strategy for post-operative recurrence prevention of cancer.

Modifying living cells using in-situ synthesized nanomaterials to endow them with new functions is highly desirable. Herein we report intra- and extra-cellular dual-modified red blood cells (RBCs) with intracellular CaCO 3 nanoparticles (NPs) and extracellular polypyrrole-folic acid (PPy-FA) coating, which are exploited as a bifunctional drug carrier. The functionalized living cells (CaCO 3 @RBC@PPy-FA) are fabricated through first the intracellular in situ reaction of exogenous Ca2+ and CO 3 2− ions to generate CaCO 3 NPs, then polymerization of pyrrole and finally modification of folic acid (FA) on the membrane of individual cells, forming a CaCO 3 @RBC@PPy-FA structure. As a result, such dual-modified RBCs not only preserve the original performances of the cells but also possess the desirable properties as a drug carrier, such as high loading capacity due to the action of CaCO 3 NPs, targeting and light-controlled drug release due to the action of PPy-FA. Under NIR laser stimulation, these bifunctional RBCs (DOX-CaCO 3 @RBC@PPy-FA) present an instant release profile of doxorubicin (DOX) and have high targeting-ability toward cancer cells, achieving a marked synergistic combined photothermal–chemotherapy effect. • Bifunctional red blood cells were formed via intra- and extra-cellular modifications. • Intracellular CaCO 3 nanoparticles and extracellular polypyrrole-folic acid coating • High loading capacity and light-controlled drug release were achieved. • Bifunctional red blood cells were used for combined photothermal-chemotherapy. [ABSTRACT FROM AUTHOR]

A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD-modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus-specific penetrated delivery together with photothermal therapy-mediated chemosensitization and photothermal therapy-strengthened integrin targeting-based antimigration. In vitro and in vivo data verified the mechanism of the tumor-selective infiltration of IPHG is based on a rigid 2D structure-associated advantage regarding hemodynamics and endothelial contact, followed by iRGD-endowed transendothelial and intratumoral transport. Once IPHG-DOX-penetrated 4T1 tumors are exposed to near-infrared irradiation, hyperthermia stress and photothermal therapy-elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy., (© 2021 Wiley-VCH GmbH.)

The development of smart size-tunable drug delivery nanoplatform enables the solving of the paradox of inconsistent size-dependence of high tumor accumulation and deep penetration during its delivery process, thus achieving superior cancer treatment efficacy. Herein, we report a size-shrinkable nanomicelle complex system with an initial size of 101 nm enabling effective retention around the tumor periphery and could destruct to ultrasmall nanomicelles triggered by a near-infrared (NIR) laser to realize the deep tumor penetration. The nanomicelle system is consisted of an upper critical solution temperature (UCST)-type block copolymer poly(acrylamide-acrylonitrile)-polyethylene glycol-lipoic acid (p(AAm- co -AN)- g -PEG-LA) encapsulating gold nanorods. Upon the irradiation of the NIR laser at the tumor site, gold nanorods could convert the light energy to heat energy, realizing the photothermal ablation of superficial tumor tissue. Concurrently, the large micelles split into a cascade of ultrasmall micelles (∼7 nm), which could easily penetrate into the deep site of the tumor and achieve the in situ "on-demand" release of the loaded drug to exert superior combined photothermal-chemotherapy of cancer. By the precise manipulation of laser, the micelle complex system realized the hierarchical killing from the superficial-to-deep tumor and achieved almost complete tumor growth inhibition on the established xenograft liver tumor mice model.

In this article, we constructed mesoporous silica-based nanoscale platform rGO/MSN/C18PEG for phototheraml-chemotherapy, in which the mesoporous silica grew on the reduced graphene oxide (rGO) via supramolecular interaction and octadecanoic acid modified PEG (C18PEG) was introduced to improve the solubility and stability. Further, the therapeutic drug doxorubicin (DOX) was loaded into this nanoplatform through noncovalent interaction to construct rGO/MSN/C18PEG@DOX delivery system. All obtained date indicated that rGO/MSN/C18PEG@DOX exhibited uniform nanoscale size and excellent stability. Compared with single chemotherapy or photothermal therapy, rGO/MSN/C18PEG@DOX showed enhanced anticancer efficacy due to combination of photothermal-chemotherapy, outlining the potential application for cancer theranostics. Mesoporous silica-based nanoscale platform rGO/MSN/C18PEG was constructed via supramolecular interaction for phototheraml-chemotherapy. Image 1 • Mesoporous silica nanoscale platform rGO/MSN/C18PEG was constructed. • Mesoporous silica grew on reduced graphene oxide via supramolecular interaction. • C18PEG was introduced to improve the solubility and stability. • DOX was loaded into rGO/MSN/C18PEG by noncovalent interaction. • rGO/MSN/C18PEG@DOX showed enhanced anticancer efficacy under light irradiation. [ABSTRACT FROM AUTHOR]

Rational design and construction of theranostic nanomedicines based on clinical characteristics of cervical cancer is an important strategy to achieve precise cancer therapy. Herein, we fabricate a cervical cancer-targeting gold nanorod-mesoporous silica heterostructure for codelivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin-AuNRs@SiO 2 -Avastin@PEI/AE105) to achieve synergistic chemophotothermal therapy. Based on database analysis and clinical sample staining, conjugation of the AE105-targeting peptide obviously improves the intracellular uptake of the nanosystem and enhances the cancer-killing ability and selectivity between cervical cancer and normal cells. It could also be used to specifically monitor the urokinase-type plasminogen activator receptor (uPAR) expression level in clinical cervical specimens, which would be an early indicator of prognosis in cancer treatment. Under 808 nm laser irradiation, the nanosystem demonstrates smart NIR-light-triggered drug release and prominent photodynamic activity via induction of reactive oxygen species overproduction-mediated cell apoptosis. The nanosystem also simultaneously suppresses HeLa tumor growth and angiogenesis in vivo, with no evident histological damage observed in the major organs. In short, this study not only provides a clinical data-based rational design strategy of smart nanomedicine for precise treatment and rapid clinical diagnosis of cervical cancer but also contributes to the development of the clinical translation of nanomedicines.

Recently, nano-sized ultrasound contrast agents encapsulating drugs for cancer diagnosis and therapy have attracted much attention. However, the ultrasound signal of these agents is too weak to obtain an ideal ultrasound imaging effect. Furthermore, conventional ultrasound contrast agents with strong echo signal are not suitable for drug delivery against cancer because of their large size. To circumvent this problem, phase-transition ultrasound contrast agents are believed to be an excellent choice. Methods: Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC) were synthesized by film dispersion method. The morphology, particle size, and stability of these liposomes (DHPL) were investigated. The photothermal effect, drug release, particle size change, cytotoxicity, and ultrasound imaging were studied by using the near infrared (NIR) light. Furthermore, tumor accumulation of DHPL was observed by in vivo fluorescence imaging and the antitumor effect was verified in a 4T1 tumor model. Results: The nanosystem displayed a homogeneous size distribution (~200 nm) and an efficient light-to-heat conversion effect under 808 nm NIR laser irradiation. The nanometer size enabled considerable accumulation of DHPL in the tumor sites. The localized hyperthermia resulting from the photothermal effect of HAuNS could trigger the size transformation of DHPL followed by significant DOX release. Due to the gasification of PFC, a remarkably enhanced ultrasound signal was detected. DHPL also exhibited a prominent photothermally reinforced chemotherapeutic effect under the control of NIR light both in vitro and in vivo . Importantly, no systemic toxicity was observed by DHPL treatment. Conclusion: In this study, we fabricated multi-functional perfluorocarbon liposomes for ultrasound imaging-guided photothermal chemotherapy which have the potential to serve as a prospective cancer treatment approach., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Cu@Cu 2 O@PSMA polymer nanoparticles (Cu@Cu 2 O@polymer NPs) with near-infrared (NIR) absorption were successfully synthesized in a single-step oxidation reaction of Cu@PSMA polymer NPs at 100 °C for 20 min. The shape, structure, and optical properties of the Cu@Cu 2 O@polymer NPs were tailorable by controlling the reaction parameters, for example, using the initial Cu@PSMA polymer NP as a template and varying the halide ion content, heating temperature, and reaction time. The Cu@Cu 2 O@polymer NPs exhibited robust NIR absorption between 650 and 710 nm and possessed superior oxidation resistance in water and culture media. In vitro assays demonstrated the low cytotoxicity of the Cu@Cu 2 O@PSMA polymer NPs to HeLa cells through an improved cell viability, high IC 50 , low injury incidence from the supernatant of the partly dissociated Cu@Cu 2 O@PSMA polymer NPs, and minor generation of reactive oxygen species. More importantly, we demonstrated that the inorganic Cu-based nanocomposite [+0.34 V vs normal hydrogen electrode (NHE)] was degradable in an endogenous H 2 O 2 (+1.78 V vs NHE) environment. Cu ions were detected in the urine of mice, which illustrates the possibility of extraction after the degradation of the Cu-based particles. 'After an treatment of the HeLa cells with the Cu@Cu 2 O@polymer NPs and a 660 nm light-emitting diode, the photoablation of 50 and 90% cells was observed at NP doses of 20 and 50 ppm, respectively. These results demonstrate that NIR-functional and moderate redox-active Cu@Cu 2 O@polymer NPs are potential next-generation photothermal therapy (PTT) nanoagents because of combined features of degradation resistance in the physiological environment, enabling the delivery of efficient PTT, a possibly improved ability to selectively harm cancer cells by releasing Cu ions under high-H 2 O 2 and/or low-pH conditions, and ability to be extracted from the body after biodegradation.

Folate-targeted gold nanorods (GNRs) are proposed as selective theranostic agents for osteosarcoma treatment. An amphiphilic polysaccharide based graft-copolymer (INU-LA-PEG-FA) and an amino derivative of the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide functionalized with folic acid (PHEA-EDA-FA), have been synthesized to act as coating agents for GNRs. The obtained polymer-coated GNRs were characterized in terms of size, shape, zeta potential, chemical composition, and aqueous stability. They protected the anticancer drug nutlin-3 and were able to deliver it efficiently in different physiological media. The ability of the proposed systems to selectively kill tumor cells was tested on U2OS cancer cells expressing high levels of FRs and compared with human bronchial epithelial cells (16HBE) and human dermal fibroblasts (HDFa). The property of the nanosystems of efficiently controlling drug release upon NIR laser irradiation and of acting as an excellent hyperthermia agent as well as Two Photon Luminescence imaging contrast agents was demonstrated. The proposed folate-targeted GNRs have also been tested in terms of chemoterapeutic and thermoablation efficacy on tridimensional (3-D) osteosarcoma models.

To track nanocarriers, many researches adopt nanocarriers labeled with radiotracers or encapsulating near-infrared fluorescence (NIRF) dye. In this study, novel amphiphilic copolymers, methoxy poly(ethylene glycol) (mPEG)-cyanine-poly(ε-caprolactone) (PCL) (mPEG-Cy-PCL) are synthesized. mPEG-Cy-PCL are capable of performing NIRF imaging, photothermal therapy (PTT) on cancer cells and self-assembly nanocarriers. Cy-based micelles can encapsulate doxorubicin (Doxo@Cy-micelle) and achieve NIRF image-guided drug delivery. Doxo@Cy-micelles are nanosized micelles enhancing the accumulation of Doxo in tumor sites and decreasing side effects. Doxo@Cy-micelles exhibit an excellent PTT and synergistic chemotherapy of cancer via laser-triggered release of Doxo from micelles, eventually resulting in decreased cancer recurrence rates. The results show that Cy-based micelles are excellent nanocarriers for NIRF imaging and synergistic photothermal-chemotherapy of cancer., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)