Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

NIR absorptive croconic acid/quercetin/CaO2 nanoplatform for tumor calcium overload therapy combined mild photothermal therapy.

With excellent biocompatibility, stable chemical and optical properties, small organic molecules-based agents have always been a research hotspot in cancer photothermal therapy (PTT). In this work, a novel croconic acid-based molecule (CR) was designed and synthesized as an ideal photothermal agent (PTA), which showed abundant near-infrared (NIR) light absorption, high photothermal conversion ability, and excellent photothermal stability. By loading CR and quercetin (Qu) in CaO2, and coated with DSPE-PEG2000, a multifunctional theranostic nanoparticle (CCQ) was successfully prepared for calcium overloading mitochondrial metabolism inhibition synergetic mild PTT. Upon entering tumor microenvironment, CCQ can produce abundant H2O2 and a large amount of calcium ions, which lead to the imbalance of calcium concentration in the internal environment of tumor cells and induced mitochondrial apoptosis. With the existence of Qu, CCQ can effectively inhibit the expression of heat shock proteins (Hsp) during the PTT process, which weaken the heat resistance of tumors, ablate tumors at lower temperature (~45 °C), and reduce the damage to normal tissues. Guided by photoacoustic imaging (PAI), CCQ showed excellent multimodal therapeutic effect of tumors. This study provided a novel CR organic molecule-based theranostic nanoplatform that can be used to treat tumors via calcium overload therapy synergetic PTT at safe temperatures, which has promising potential for the future clinical cancer treatment.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.