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Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs. Additionally, nanoparticles composed from only the photothermal polymer, poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), were also coated with HA, to form HA-BSe NPs, and evaluated in 3D. Monitoring of nanoparticle transport in 3D organoids revealed uniform diffusion of non-targeted HDAPPs in comparison to attenuated diffusion of HA-HDAPPs due to nanoparticle-matrix interactions. Computational diffusion profiles suggested that HA-HDAPPs transport may not be accounted for by diffusion alone, which is indicative of nanoparticle/cell matrix interactions. Photothermal activation revealed that only HA-BSe NPs were able to significantly reduce tumor cell viability in the organoids. Despite limited transport of the CD44-targeted theranostic nanoparticles, their targeted retention provides increased heat for enhanced photothermal ablation in 3D, which is beneficial for assessing nanoparticle therapies prior to in vivo testing.

Theranostic nanoplatforms integrating fluorescence imaging and photothermal therapy have shown great potential in cancer research for tumor detection and image-guided treatment. Herein, a unique th...

Hyperthermia has shown tremendous therapeutic efficiency in the treatment of cancer due to its controllability, minimal invasiveness and limited side effects compared to the conventional treatment techniques like surgery, radiotherapy and chemotherapy. To improve the precision of hyperthermia specifically to a tumor location, near infra-red (NIR) light activatable inorganic metal nanoparticles have served as effective photothermal therapy materials, but toxicity and non-biodegradability have limited their clinical applications. Conjugated polymer nanoparticles have overcome these limitations and are emerging as superior photothermal materials owing to their excellent light harvesting nature, biocompatibility and tunable absorption properties. In this review we focus on the development of organic conjugated polymers (polyaniline, polypyrrole, polydopamine etc.) and their nanoparticles, which have broad NIR absorption. Such materials elicit photothermal effects upon NIR stimulation and may also serve as carriers for delivery of therapeutic and contrast agents for combined therapy. Subsequently, the emergence of donor-acceptor based semiconducting polymer nanoparticles with strong absorbance that is tunable across the NIR have been shown to eradicate tumors by either hyperthermia alone or combined with other therapies. The design of multifunctional polymer nanoparticles that absorb near- or mid- infrared light for heat generation, as well as their diagnostic abilities for precise biomedical applications are highlighted.

Nanoparticles offer many promising advantages for improving current surgical regimens through their ability to detect and treat disseminated colorectal cancer (CRC). Hybrid Donor-Acceptor Polymer Particles (HDAPPs) have recently been shown to fluorescently detect and thermally ablate tumors in a murine model. Here, HDAPPS were functionalized with hyaluronic acid (HA) to improve their binding specificity to CT26 mouse CRC cells using HA to target the cancer stem cell marker CD44. In this work, we compared the binding of HA functionalized HDAPPs (HA-HDAPPs) in in vitro, ex vivo, and in vivo environments. The HA-HDAPPs bound to CT26 cells 2-fold more in vitro and 2.3-fold higher than un-functionalized HDAPPs ex vivo. Compared to intraoperative abdominal perfusion, intraperitoneal injection prior to laser stimulation for nanoparticle heat generation provides a superior modality of HA-HDAPPs delivery for CRC tumor selectivity. Photothermal treatment of disseminated CRC showed that only HA-HDAPPs delivered via intraperitoneal injection had a reduction in the tumor burden, and these nanoparticles also remained in the abdomen following resolution of the tumor. The results of this work confirm that HA-HDAPPs selectively bind to disseminated CRC, with ex vivo tumors having bound HA-HDAPPs capable of photothermal ablation. HA-HDAPPs demonstrated superior binding to tumor regions compared to HDAPPs. Overall, this study displays the theranostic potential of HDAPPs, emphasizing their capacity to detect and photothermally treat disseminated CRC tumors.

Judicious combination of semiconducting polymers with alternating electron donor (D) and acceptor (A) segments created hybrid nanoparticles with amplified energy transfer and red-shifted emission, while simultaneously providing photothermal capabilities. Hybrid D-A polymer particles (H-DAPPs) passively localized within orthotopic breast tumors, serving as bright fluorescent beacons. Laser stimulation induced heat generation on par with gold nanorods, resulting in selective destruction of the tumor. H-DAPPs can also undergo multiple thermal treatments, with no loss of fluorescence intensity or photothermal potential. These results indicate that H-DAPPs provide new avenues for the synthesis of hybrid nanoparticles useful in localized detection and treatment of disease.

Background and Objective Photothermal therapy (PTT) has several applications in the areas of wound healing, pain management, bacterial infection control, and cancer treatment dependent on the temperature that is generated. PTT is often used exclusively with near infrared (NIR) light and most nanoparticles (NP) used for PTT are designed to absorb within one narrow range of wavelengths. We have developed a dual-wavelength photothermal therapy by capitalizing on the dual absorption of nanoparticles in the blue and NIR range. Materials and Methods Our lab has previously developed NP based on the semiconducting, conjugated polymer poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b′]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). The NP have strong absorption in the blue and NIR regions. In this report, we have explored the heat generated by PCPDTBSe NP using simultaneous delivery of 450 and 800 nm light, either independently or together for photothermal ablation of mouse colorectal cancer cells. Results The heat generation studies indicated that the use of either 450 or 800 nm wavelengths at the same fluences produced approximately the same temperature change of deionized water. Fluences of 114.6 and 229.2 J/cm2, utilizing 450 or 800 nm light applied individually resulted in temperatures of 8–47°C above ambient temperature, leading to a 90% reduction in cell viability. Simultaneous stimulation of the PCPDTBSe NP with 450 and 800 nm light effectively doubles the effective power delivered, resulting in temperatures 18–63°C above ambient and 100% photothermal ablation of the colorectal cancer cells. Conclusion The results of this study demonstrate that PCPDTBSe polymer NP can be utilized as effective PTT agents by capitalizing on their dual absorption of both blue and NIR light. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc.

The aim of this study was to demonstrate that multi-wall carbon nanotubes can be functionalised with antibodies to group A streptoccocus (GAS) for targeted photothermal ablation of planktonic and biofilm residing bacteria.Antibodies for GAS were covalently attached to carboxylated multi-wall carbon nanotubes and incubated with either planktonic or biofilm GAS. Bacterium was then exposed to 1.3 W/cm(2) of 800 nm light for 10-120 s, and then serially diluted onto agar plates from which the number of colony forming units was determined. Photothermal ablation of GAS on the surface of full thickness ex vivo porcine skin and histological sectioning were done to examine damage in adjacent tissue.Approximately 14% of the GAS antibody-functionalised nanotubes attached to the bacterium, and this amount was found to be capable of inducing photothermal ablation of GAS upon exposure to 1.3 W/cm(2) of 800 nm light. Cell viability was not decreased upon exposure to nanotubes or infrared light alone. Compared to carboxylated multi-wall carbon nanotubes, antibody-labelled nanotubes enhanced killing in both planktonic and biofilm GAS in conjunction with infrared light. Analysis of GAS photothermally ablated in direct contact with ex vivo porcine skin shows that heat sufficient for killing GAS remains localised and does not cause collateral damage in tissue adjacent to the treated area.The results of this study support the premise that carbon nanotubes may be effectively utilised as highly localised photothermal agents with the potential for translation into the clinical treatment of bacterial infections of soft tissue.

The photothermal efficiency of two similar organic nanomaterials, poly(3,4-ethylenedioxythiophene):poly(4-styrene-sulfonate) (PEDOT:PSS) nanoparticles and poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes, are compared. The PEDOT:PSS nanoparticles ranged from 100-200 nm in diameter, while the PEDOT nanotubes ranged from 200-400 nm in diameter and 4-10 microm in length. By changing the aspect ratio of the PEDOT nanomaterials from a spherical to a tubular shape, interesting differences in the optical and electronic properties of the materials were realized. Because of this, the PEDOT nanotubes were shown to generate on average approximately to 10 degrees C better internal heating for similar concentrations compared to the PEDOT:PSS nanoparticles. Cytotoxicity studies of both nanomaterials showed no significant toxicity towards RKO or HCT116 colorectal cancer cells in the absence of NIR light. The NIR-mediated photothermal efficiency of the PEDOT:PSS nanoparticles and the PEDOT nanotubes were compared in-vitro. A cell viability assay was performed and at the highest concentration (0.1 mg/mL) of nanomaterial, cell survival was close to 20% for the PEDOT:PSS nanoparticles with both RKO and HCT116 cells. Consequently, cell survival for the PEDOT nanotubes was less than 5% for both RKO and HCT116 cells. An in-vitro three dimensional tumor model was assembled using collagen gel tissue phantoms. The depth of heat penetration from the PEDOT nanotubes into the tissue phantoms, along with cell viability of RKO and HCT116 cells was determined and quantified.

Peritoneal metastases of colorectal cancer are a significant challenge in the field of medicine today due to poor results of systemic chemotherapy caused by the poor diffusion of drugs across the blood–peritoneal barrier. Multi-walled carbon nanotubes (MWNTs) are a biocompatible nanomaterial that strongly absorb near-infrared light to locally heat the surrounding area. Colorectal cancer is known to overexpress folate receptor; therefore, folic acid (FA) was covalently attached to MWNTs to target colorectal cancer cells. Results from real-time polymerase chain reaction found differing expression of folate receptor-α in two colorectal cancer cell lines, RKO and HCT116, as well as a healthy epithelial cell line, HEPM. A spectrophotometric method was developed to quantify the mass of MWNTs bound to cells, and it was determined that FA-targeted MWNTs resulted in a 400–500 % greater affinity for colorectal cancer cells than untargeted MWNTs. The non-cancerous cell line, HEPM, had higher non-specific MWNT interaction and similar MWNT–FA affinity. Stimulated by 1,064 nm light, FA-functionalized MWNTs caused a 50–60 % decrease in colorectal cancer cell viability compared to a 4–10 % decrease caused by untargeted MWNTs. Our results indicate that FA-targeted MWNTs may increase the therapeutic index of MWNT-induced photothermal therapy.

Low band gap D-A conjugated PNs consisting of 2-ethylhexyl cyclopentadithiophene co-polymerized with 2,1,3-benzothiadiazole (for nano-PCPDTBT) or 2,1,3-benzoselenadiazole (for nano-PCPDTBSe) have been developed. The PNs are stable in aqueous media and showed no significant toxicity up to 1 mg · mL(-1) . Upon exposure to 808 nm light, the PNs generated temperatures above 50 °C. Photothermal ablation studies of the PNs with RKO and HCT116 colorectal cancer cells were performed. At concentrations above 100 µg · mL(-1) for nano-PCPDTBSe, cell viability was less than 20%, while at concentrations above 62 µg · mL(-1) for nano-PCPDTBT, cell viability was less than 10%. The results of this work demonstrate that low band gap D-A conjugated polymers 1) can be formed into nanoparticles that are stable in aqueous media; 2) are non-toxic until stimulated by IR light and 3) have a high photothermal efficiency.

Multiwalled carbon nanotubes (MWCNTs) exhibit physical properties that render them ideal candidates for application as noninvasive mediators of photothermal cancer ablation. Here, we demonstrate that use of MWCNTs to generate heat in response to near-infrared radiation (NIR) results in thermal destruction of kidney cancer in vitro and in vivo. We document the thermal effects of the therapy through magnetic resonance temperature-mapping and heat shock protein-reactive immunohistochemistry. Our results demonstrate that use of MWCNTs enables ablation of tumors with low laser powers (3 W/cm 2 ) and very short treatment times (a single 30-sec treatment) with minimal local toxicity and no evident systemic toxicity. These treatment parameters resulted in complete ablation of tumors and a >3.5-month durable remission in 80% of mice treated with 100 μg of MWCNT. Use of MWCNTs with NIR may be effective in anticancer therapy.

Carbon nanotubes are unique materials that absorb infrared (IR) radiation, especially between 700 and 1100 nm, where body tissues are most transparent. Absorbed IR promotes molecular oscillation leading to efficient heating of the surrounding environment. A method to enhance drug localization for peritoneal malignancies is perfusion of warm (40-42 degrees C) chemotherapeutic agents in the abdomen. However, all tissues in the peritoneal cavity are subjected to enhanced drug delivery due to increased cell membrane permeability at hyperthermic temperatures. Here we show that rapid heating (within ten seconds) of colorectal cancer cells to 42 degrees C, using infrared stimulation of nanotubes as a heat source, in the presence of the drugs oxaliplatin or mitomycin C, is as effective as two hours of radiative heating at 42 degrees C for the treatment of peritoneal dissemination of colorectal cancer. We demonstrate increased cell membrane permeability due to hyperthermia from multiwalled carbon nanotubes in close proximity to cell membranes and that the amount of drug internalized by colorectal cancer cells heated quickly using carbon nanotubes equals levels achieved during routine application of hyperthermia at 42 degrees C. This approach has the potential to be used as a rapid bench to bedside clinical therapeutic agent with significant impact for localizing chemotherapy agents during the surgical management of peritoneal dissemination of colorectal cancer.

The aim of this review is to provide an up-to-date overview of nanoparticles developed for use as photothermal therapy agents (PTT) over the past five years. The main emphasis is on nanoparticles that absorb near infrared (NIR) light for PTT of cancer. Mild hyperthermia, including drug delivery, versus thermal ablation is also discussed. Recent advances in the synthesis of highly anisotropic novel metal nanoparticles for PTT are described. New metals and metal oxide complexes, as well as the use of quantum dots for PTT and as imaging agents are newer areas of development that are explained. This review also highlights current progress in the development of carbon nanoparticles, including reduced graphene oxide for both thermal ablation as well as drug delivery. The review culminates in the recent use electrically conductive polymer nanoparticles for hyperthermia. The advantages and unique features of these contemporary nanoparticles being used for PTT are highlighted. The goal of the present work is to describe the recent evolution of nanoparticles for NIR stimulated PTT, and highlight the innovations and future directions.

Nanotubes (NT) composed of the electrically active polymer poly (3,4-ethylenedioxythiophene) (PEDOT) have been used for photothermal ablation of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. Since infrared absorption of PEDOT is dominated by bipolarons strongly coupled to phonons, we hypothesize that nonradiative decay of these states leads to heat generation. Photothermal death of bacteria by PEDOT NT was compared to single-wall carbon nanotubes (SWNT). Complete eradication of bacterial colonies incubated with 100 ug/ml of either PEDOT NT or SWNT occurred with a single exposure to 1064 nm light (3.8 W/cm2) for 60 s. PEDOT NT were also shown to elicit a mild antibacterial response upon incubation with bacteria and no infrared exposure. PEDOT NT have the same capacity for photothermal ablation of bacteria as compared to SWNT; therefore, they represent an exciting new class of polymer based nanoparticles for medically-relevant photothermal therapies.