Search

Combining phototherapy with other treatments has significantly advanced cancer therapy. Here, we designed and fabricated calcium-enriched carbon nanoparticles (Ca-CNPs) that could effectively deplete glutathione (GSH) and release calcium ions in tumors, thereby enhancing the efficacy of photodynamic therapy (PDT) and the calcium overload effect that leads to mitochondrial dysfunction. Due to the electrostatic interaction, π-π stacking interaction, multiple hydrogen bonds, and microporous structures, indocyanine green (ICG) was loaded onto the surface of Ca-CNPs with a high loading efficiency of 44.7 wt%. The obtained Ca-CNPs@ICG can effectively improve the photostability of ICG while retaining its ability to generate singlet oxygen ( 1 O 2 ) and undergo photothermal conversion (Ca-CNPs@ICG vs. ICG, 45.1% vs. 39.5%). In vitro and in vivo experiments demonstrated that Ca-CNPs@ICG could be used for near-infrared fluorescence imaging-guided synergistic calcium overload, photothermal therapy, and GSH depletion-enhanced PDT. This study sheds light on the improvement of 1 O 2 utilization efficiency and calcium overload-induced mitochondrial membrane potential imbalance in tumor cells.

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer (PT2) and a two-dimensional pleated niobium carbide (Nb2C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb2C MXene through electrostatic interaction to obtain Nb2C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb2C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H 2 O 2 ) to produce O 2 , in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H 2 O 2 further results in abnormal cellular H 2 O 2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy.

Vascular disruption agent (combretastatin A-4 phosphate) and phototherapeutic (IEICO-4F) assembled nanoparticles (IFC NPs) were prepared for the first time. The IFC NPs have a high photo energy utilization efficiency of up to 96.1%, and could significantly inhibit tumor growth by photodynamic and photothermal therapy enhanced tumor vascular disruption.

Phototherapeutic agents with near-infrared (NIR) fluorescence, strong reactive oxygen species generation and photothermal conversion capabilities are highly desirable for use in cancer therapy. Herein, a water-soluble NIR croconaine dye (TCR) with a thiophene-croconaine rigid core and two symmetric alkyl chains was designed and synthesized. TCR exhibits intense NIR absorption and fluorescence that peaked at 780 and 815 nm, respectively, with a high molar extinction coefficient of 1.19 × 10 5 M -1 cm -1 . Moreover, TCR has a high photothermal conversion efficiency of 77% and is capable of generating hydroxyl radicals (OH˙) under 735 nm laser irradiation. Based on these outstanding properties, TCR has proven its application in NIR fluorescence imaging-guided synergistic photothermal/photodynamic therapy of cancer.

Nanosheet carriers loaded with drugs and phototherapeutics are used for effective cancer therapy, but the process remains challenging. Here, we prepared sulfur nanosheets (S-NSs) and then loaded tirapazamine (TPZ) and indocyanine green (ICG) with a loading efficiency of 6.3% and 94%, respectively. The obtained S-NSs-TPZ-ICG exhibits near-infrared (NIR) fluorescence, high 1 O 2 generation and photothermal conversion capabilities, good biocompatibility, and tumor microenvironment responsiveness. In vivo and in vitro experiments reveal that S-NSs-TPZ-ICG can be selectively decomposed under acidic and H 2 O 2 conditions to release TPZ and ICG, and significantly inhibit tumor growth under laser irradiation without obvious toxic side effects.

Image-guided photodynamic therapy (PDT) has received growing attention due to its non-invasiveness and precise controllability. However, the PDT efficiency of most photosensitizers are decreased in living system due to the aggregation-caused singlet oxygen ( 1 O 2 ) generation decreasing. Herein, we present an Iridium (III) pyridylpyrrole complex (Ir-1) featuring of aggregation-induced emission (AIE) and 1 O 2 generation characteristics for image-guided PDT of cancer. Ir-1 aqueous solution exhibits bright red phosphorescence peaked at 630 nm, large Stokes shift of 227 nm, and good 1 O 2 generation ability. The 1 O 2 generating rate of Ir-1 in EtOH/water mixture solution is 2.3 times higher than that of Rose Bengal. In vitro experimental results revealed that Ir-1 has better biocompatibility and higher phototoxicity compared with clinically used photosensitizers (Rose Bengal and Ce6), suggesting that Ir-1 can serve as a photosensitizer for image-guided PDT of cancer., (© 2021 Wiley-VCH GmbH.)

Nanocarrier-based drug delivery systems hold impressive promise for biomedical application because of their excellent water dispersibility, prolonged blood circulation time, increased drug accumulation in tumors, and potential in combination therapeutics. However, most nanocarriers suffer from low drug-loading efficiency, poor therapeutic effectiveness, potential systematic toxicity, and unstable metabolism. As an alternative, carrier-free nanodrugs, completely formulated with one or more drugs, have attracted increasing attention in cancer therapy due to their advantage of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug-loading. In recent years, carrier-free nanodrugs have contributed to progress in a variety of therapeutic modalities. In this review, different common strategies for carrier-free nanodrugs preparation are first summarized, mainly including nanoprecipitation, template-assisted nanoprecipitation, thin-film hydration, spray-drying technique, supercritical fluid (SCF) technique, and wet media milling. Then we describe the recently reported carrier-free nanodrugs for cancer chemo-monotherapy or combination therapy. The advantages of anti-cancer drugs combined with other chemotherapeutic, photosensitizers, photothermal, immunotherapeutic or gene drugs have been demonstrated. Finally, a future perspective is introduced to highlight the existing challenges and possible solutions toward clinical application of currently developed carrier-free nanodrugs, which may be instructive to the design of effective carrier-free regimens in the future., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

As an emerging clinical modality for cancer treatment, photodynamic therapy (PDT) takes advantage of the cytotoxic activity of reactive oxygen species (ROS) that are generated by light irradiating photosensitizers (PSs) in the presence of oxygen (O 2 ). However, further advancements including tumor selectivity and ROS generation efficiency are still required. Substantial efforts are devoted to design and synthesize smart PSs with optimized properties for achieving a desirable therapeutic efficacy. This review summarizes the recent progress in developing intelligent PSs for efficient PDT, ranging from single molecules to delicate nanomaterials. The strategies to improve ROS generation through optimizing photoinduced electron transfer and energy transfer processes of PSs are highlighted. Moreover, the approaches that combine PDT with other therapeutics (e.g., chemotherapy, photothermal therapy, and radiotherapy) and the targeted delivery in cancer cells or tumor tissue are introduced. The main challenges for the clinical application of PSs are also discussed., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)