Monolayer LDH Nanosheets with Ultrahigh ICG Loading for Phototherapy and Ca2+-Induced Mitochondrial Membrane Potential Damage to Co-Enhance Cancer Immunotherapy.

Tumor recurrence and metastasis are the main causes of cancer mortality; traditional chemotherapeutic drugs have severe toxicity and side effects in cancer treatment. To overcome these issues, here, we present a pH-responsive, self-destructive intelligent nanoplatform for magnetic resonance/fluorescence dual-mode image-guided mitochondrial membrane potential damage (MMPD)/photodynamic (PDT)/photothermal (PTT)/immunotherapy for breast cancer treatment with external near infrared (NIR) light irradiation. To do so, we construct multifunctional monolayer-layered double hydroxide (LDH) nanosheets (MICaP), co-loading indocyanine green (ICG) with ultrahigh loading content realized via electrostatic interactions, and calcium phosphate (Ca3(PO4)2) coating via biomineralization. Such a combined therapy design is featured by the outstanding biocompatibility and provokes immunogenic cell death (ICD) of tumors toward cancer immunotherapy. The active transport of excess Ca2+ released from pH-sensitive Ca3(PO4)2 can induce MMPD of tumor cells to minimize oxygen consumption in the tumor microenvironment (TME). The presence of ICG not only generates singlet oxygen (1O2) to induce apoptosis by photodynamic therapy (PDT) but also initiates tumor cell necrosis by photothermal therapy (PTT) under near-infrared (NIR) light radiation. Eventually, the immune response generated by MMPD/PDT/PTT greatly promotes a cytotoxic T lymphocyte (CTL) response that can limit tumor growth and metastasis. Both in vitro and in vivo studies indeed illustrate outstanding antitumor efficiency and outcomes. We anticipate that such precisely designed nanoformulations can contribute in a useful and advantageous way that is conducive to explore novel nanomedicines with notable values in antitumor therapy.

Starvation-assisted and photothermal-thriving combined chemo/chemodynamic cancer therapy with PT/MR bimodal imaging.

Chemodynamic therapy (CDT) reflects a novel reactive oxygen species (ROS)-related cancer therapeutic approach. However, CDT monotherapy is often limited by weak efficacy and insufficient endogenous H2O2. Herein, a multifunctional combined bioreactor (MnFe-LDH/MTX@GOx@Ta, MMGT) relying on MnFe-layered double hydroxide (MnFe-LDH) loaded with methotrexate (MTX) and coated with glucose oxidase (GOx)/tannin acid (Ta) is established for applications in H2O2 self-supply and photothermal enhanced chemo/chemodynamic combined therapy along with photothermal (PT) /magnetic resonance (MR) dual-modality imaging ability for cancer treatment. Once internalized into tumor cells, MMGT achieves starvation therapy by catalyzing the oxidation of glucose with GOx, accompanied by the regeneration of H2O2, enabling a Fenton-like reaction to accomplish GOx catalytic amplified CDT. Moreover, MMGT manifests significant tumor-killing ability through improved CDT performance with outstanding photothermal conversion efficiency (η = 52.2%) under 808 nm laser irradiation. In addition, the release of Mn2+ from MnFe-LDH in a solid tumor can significantly enhance T1-contrast MR imaging signals. Combined with MnFe-LDH-induced PT imaging under 808 nm laser irradiation, a dual-modality imaging directed theranostic nanoplatform has been developed. The present study provides a new strategy to design H2O2 self-supply and ROS evolving NIR light-absorption theranostic nanoagent for highly efficient and combined chemo/chemodynamic cancer treatment.