Multifunctional and multimodality theranostic nanomedicine for enhanced phototherapy.

Photodynamic therapy (PDT) has attracted much attention in recent years for its favorable therapeutic efficacy in cancer therapy. However, PDT alone is insufficient to improve the therapeutic efficiency mainly due to the limited penetration depth of light, the insufficient O2 supply in the hypoxic microenvironment, and the high level of reducing substances in cancer cells. To overcome these limitations, a multifunctional MnO2 nanoparticle was constructed with honeycomb MnO2 which was loaded with the photosensitizer Ce6 and modified with polydopamine on its surface (HMnO2/C&P) to achieve efficient PDT/mild photothermal treatment (PTT) combination therapy. HMnO2/C&P had high drug loading contents (11.2% Ce6) and can be responsive to the tumor microenvironment (TME), supply O2 to alleviate the hypoxic microenvironment, and clear GSH to reduce the consumption of ROS, thus enhancing the PDT effect. The introduction of PDA can improve the stability of HMnO2/C&P, and further give the ability of PTT to act as nanomedicine. The results of in vitro and in vivo experiments show that HMnO2/C&P based PDT/mild PTT combination therapy has an excellent inhibitory effect on tumor growth. Meanwhile, HMnO2/C&P can act as a fluorescence imaging reagent and a TME triggerable magnetic resonance imaging (MRI) contrast agent, thus having excellent multimodal self-tracking abilities. Collectively, this study provides a new perspective on the design of multifunctional theranostic nanomedicine to maximize the efficacy of cancer phototherapy.

Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.

Deep Tumor Penetrating Gold Nano-Adjuvant for NIR-II-Triggered In Situ Tumor Vaccination.

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.

In vitro antioxidant and antitumor study of zein/SHA nanoparticles loaded with resveratrol.

Resveratrol (RES) loaded Zein-SHA (low-molecular-weight sodium hyaluronate) nanoparticles with average diameter of about 152.13 nm and polydispersity index (PDI) of 0.122, which can be used to encapsulate, protect and deliver resveratrol. By measuring ABTS free radical scavenging ability and iron (III) reducing power, it was determined that encapsulated resveratrol has higher in vitro antioxidant activity than free resveratrol. When tested with murine breast cancer cells 4T1, the encapsulated resveratrol also showed higher antiproliferative activity than free resveratrol, with IC50 values of 14.73 and 17.84 µg/ml, respectively. The colloidal form of resveratrol developed in this research may be particularly suitable for functional foods and beverages, as well as dietary supplements and pharmaceutical products.

Single-Stimulus Dual-Drug Sensitive Nanoplatform for Enhanced Photoactivated Therapy.

Photoactivated therapy has become a complementary and attractive modality for traditional cancer treatment. Herein, we demonstrated a novel single-stimulus dual-drug sensitive nanoplatform, Cur-loaded Dex-Pt(N3) nanoparticles (Cur@DPNs) for enhanced photoactivated therapy. The developed Cur@DPNs could be photoactivated by UVA light to simultaneously generate instant reactive oxygen species from Cur for fast photodynamic therapy and release lasting Pt(II) from Pt(N3) for long-acting photochemotherapy. Compared with small free drugs and individual photoactivated therapy, Cur@DPNs exhibited enhanced photoactivated cytotoxicity and in vivo antitumor efficacy with low systemic toxicity accompanied. Therefore, the single-stimulus dual-drug sensitive nanoplatform is convinced to be a promising strategy for multidrug delivery, site-selective and combinational photoactivated therapy in the near future.