Black Silver Nanocubes@Amino Acid-Encoded Highly Branched Gold Shells with Efficient Photothermal Conversion for Tumor Therapy.

Cancers are among the leading causes of death currently. Conventional radiotherapy and chemotherapy are of limited use in the treatment of some tumors due to their high toxicity and drug resistance. Plasma photothermal therapy has attracted extensive attention for the treatment of tumors due to photothermal properties of plasmonic nanoparticles, such as gold (Au) nanoparticles, to achieve local hyperthermia with low toxicity and high efficiency. Herein, we report a kind of special black noble-metal core-shell nanostructure, with silver (Ag) nanocubes as the core and amino acid-encoded highly branched Au nanorods as the shells (l-CAg@Au and d-CAg@Au). The proposed growth of l-CAg@Au and d-CAg@Au nanocomposites was an amino acid-encoded Stranski-Krastanov mode. Both l-CAg@Au and d-CAg@Au exhibited outstanding photothermal conversion compared to the core-shell structure without amino acids (Ag@Au). d-CAg@Au possessed the best photothermal conversion efficiency (87.28%) among the composite nanoparticles. The antitumor therapeutic efficacy of as-prepared samples was evaluated in vitro and in vivo, and apoptosis analysis was done via flow cytometry. This work reports novel insights for the preparation of special bimetallic branched structures and broadens the application of metal nanomaterials in photothermal tumor therapy.

Rational Design of a Robust Antibody-like Small-Molecule Inhibitor Nanoplatform for Enhanced Photoimmunotherapy.

Immune checkpoint blockade of the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway via an antibody is a potent strategy for T cell remodeling. Nevertheless, the potency of the antibody is partly compromised by its high price, instability, risk of autoimmune disease, and so forth. Small-molecule inhibitors are interesting alternatives to antibodies. However, tumor-specific delivery of small-molecule inhibitors to the target site for boosting the interruption of the PD-L1/PD-1 pathway is rarely reported. Herein, we designed a tumor-specific delivery nanoplatform that could efficiently deliver the small-molecule inhibitor to the precise target site, greatly enhancing the blocking effect of the PD-L1/PD-1 pathway. Hyaluronic acid (HA) was conjugated with chlorin e6 (Ce6), resulting in a HA-Ce6 conjugate (HC). The nanoplatform was constructed by the HC micelles with the encapsulation of small-molecule inhibitor, BMS 202 (BMS), to form BMS/HC micelles. The target property of HA, combined with the hyaluronidase-induced degradation of HA in the tumor site, enables the as-prepared micelles with tumor-specific delivery of BMS for blocking the PD-L1/PD-1 pathway. With cooperative treatment with the photosensitizer Ce6, the present therapeutic nanoplatform demonstrated excellent photoimmunotherapy for tumor regression in distant tumors and lung metastasis. This strategy of tumor-specific delivery of small-molecule inhibitors provides an effective pathway to strengthen the blocking efficacy of PD-L1/PD-1 on effective photoimmunotherapy.