Multifunctional Mesoporous Hollow Cobalt Sulfide Nanoreactors for Synergistic Chemodynamic/Photodynamic/Photothermal Therapy with Enhanced Efficacy.

The unique tumor microenvironment (TME) characteristic of severe hypoxia, overexpressed intracellular glutathione (GSH), and elevated hydrogen peroxide (H2O2) concentration limit the anticancer effect by monotherapy. In this report, glucose oxidase (GOx)-encapsulated mesoporous hollow Co9S8 nanoreactors are constructed with the coverage of polyphenol diblock polymers containing poly(oligo(ethylene glycol) methacrylate) and dopamine moieties containing methacrylate polymeric block, which are termed as GOx@PCoS. After intravenous injection, tumor accumulation, and cellular uptake, GOx@PCoS deplete GSH by Co3+ ions. GOx inside the nanoreactors produce H2O2 via oxidation of glucose to enhance •OH-based chemodynamic therapy (CDT) through the Fenton-like reaction under the catalysis of Co2+. Moreover, Co3+ ions possess catalase activity to catalyze production of O2 from H2O2 to relieve tumor hypoxia. Upon 808 nm laser irradiation, GOx@PCoS exhibit photothermal and photodynamic effects with a high photothermal conversion efficiency (45.06%) and generation capacity of the toxic superoxide anion (•O2-) for photothermal therapy (PTT) and photodynamic therapy (PDT). The synergetic antitumor effects can be realized by GSH depletion, starvation, and combined CDT, PTT, and PDT with enhanced efficacy. Notably, GOx@PCoS can also be used as a magnetic resonance imaging (MRI) contrast agent to monitor the antitumor performance. Thus, GOx@PCoS show great potentials to effectively modulate TME and perform synergistic multimodal therapy.

Oxygen-independent combined photothermal/photodynamic therapy delivered by tumor acidity-responsive polymeric micelles.

Tumor hypoxia strikingly restricts photodynamic therapy (PDT) efficacy and limits its clinical applications in cancer therapy. The ideal strategy to address this issue is to develop oxygen-independent PDT systems. Herein, the rationally designed tumor pH-responsive polymeric micelles are devised to realize oxygen-independent combined PDT and photothermal therapy (PTT) under near-infrared light (NIR) irradiation. The triblock copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-(piperidin-1-yl)ethyl methacrylate) (PEG-b-PCL-b- PPEMA), was prepared to co-encapsulate cypate and singlet oxygen donor (diphenylanthracene endoperoxide, DPAE) via self-assembly to obtain the micellar delivery system (C/O@N-Micelle). C/O@N-Micelle showed remarkable tumor accumulation and improved cellular internalization (2.1 times) as the pH value was changed from 7.4 during blood circulation to 6.8 in tumor tissues. The micelles could produce a potent hyperthermia for PTT of cypate under 808 nm NIR irradiation, which simultaneously induced thermal cycloreversion of DPAE generating abundant singlet oxygen for PDT without participation of tumor oxygen. Finally, the photothermally triggered PDT and PTT combination achieved efficient tumor ablation without remarkable systemic toxicity in an oxygen-independent manner. This work represents an efficient strategy for oxygen-independent combined PDT and PTT of cancers under NIR irradiation through co-encapsulation of cypate and DPAE into tumor pH-responsive polymeric micelles.

Near-infrared light-triggered drug release nanogels for combined photothermal-chemotherapy of cancer.

Near-infrared (NIR) light-triggered drug release systems are promising for drug delivery applications in view of the advantages of NIR light, which include high tissue penetration and low damage. In this report, we developed nanogels (NGs) by supramolecular self-assembly from adamantine (AD)-conjugated copolymer, poly[poly(ethylene glycol)monomethyl ether metharcylate]-co-poly(N-(2-hydroxypropyl)methacrylamide)-co-poly(N-adamantan-1-yl-2-methacrylamide) (PPEGMA-co-PHPMA-co-PADMA), and ß-cyclodextrin (ß-CD)-functionalized poly(amidoamine) (PAMAM) dendrimer based on the host-guest interaction of the AD and ß-CD moieties, and they were used to encapsulate indocyanine green (ICG) and doxorubicin (DOX) for combined photothermal-chemotherapy. NGs simultaneously loading ICG and DOX (DINGs) showed significant photothermal effects and stimuli-triggered drug release under NIR laser irradiation by the photothermal-induced relaxation or dissociation of the NGs. In vitro cytotoxicity evaluation of DINGs under NIR irradiation demonstrated the synergistic effects of hyperthermia, photothermal-triggered drug release, and chemotherapy. In vivo investigation revealed their high accumulation in tumor tissue and significant tumor growth suppression under NIR irradiation. These NIR light-triggered drug release NGs represent efficient and promising anticancer drug vectors for the combined photothermal-chemotherapy of cancer to maximize therapeutic efficacy and minimize side effects.