Long Circulating Cancer Cell-Targeted Bionic Nanocarriers Enable Synergistic Combinatorial Therapy in Colon Cancer.

Cancer nanomedicine treatment aims to achieve highly specific targeting and localization to cancer cells. Coating of nanoparticles with cell membranes endows them with homologous cellular mimicry, enabling nanoparticles to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused a human-derived HCT116 colon cancer cell membrane (cM) with a red blood cell membrane (rM) to fabricate an erythrocyte-cancer cell hybrid membrane (hM). Oxaliplatin and chlorin e6 (Ce6) co-encapsulated reactive oxygen species-responsive nanoparticles (NPOC) were camouflaged by hM and obtained a hybrid biomimetic nanomedicine (denoted as hNPOC) for colon cancer therapy. hNPOC exhibited prolonged circulation time and recognized homologous targeting ability in vivo since both rM and HCT116 cM proteins were maintained on the hNPOC surface. hNPOC showed enhanced homologous cell uptake in vitro and considerable homologous self-localization in vivo, producing effective synergistic chemophotodynamic therapy efficacy under irradiation with a homologous HCT116 tumor compared to that with a heterologous tumor. Together, the biomimetic hNPOC nanoparticles showed prolonged blood circulation and preferential cancer cell-targeted function in vivo to provide a bioinspired strategy for chemophotodynamic synergistic therapy of colon cancer.

Injectable hydrogel-mediated combination of hyperthermia ablation and photo-enhanced chemotherapy in the NIR-II window for tumor eradication.

Local administration of therapeutic agents with long-term retention capabilities efficiently avoids nonspecific distribution in normal organs with an increased drug concentration in pathological tissue. Herein, we developed an injectable and degradable alginate-calcium (Ca2+) hydrogel for the local administration of corn-like Au/Ag nanorods (NRs) and doxorubicin hydrochloride (DOX·HCl). The immobilized Au/Ag NRs with strong absorbance in the near-infrared II (NIR-II) window efficiently ablated the majority of tumor cells after 1064 nm laser irradiation and triggered the release of DOX to kill residual tumor cells. As a result, injectable hydrogel-mediated NIR-II photothermal therapy (PTT) and chemotherapy efficiently inhibited tumor growth, resulting in the complete eradication of tumors in most of the treated mice. Furthermore, owing to the confinement of the Au/Ag NRs and DOX·HCl within the hydrogel, such treatment exhibited excellent biocompatibility.

Photodynamic therapy produces enhanced efficacy of antitumor immunotherapy by simultaneously inducing intratumoral release of sorafenib.

Photodynamic therapy (PDT) can destroy local tumor cells and induce effective antitumor immune responses, and has been applied in the treatment of patients with superficial solid tumors. Numerous systemic side effects of PDT, such as pain and skin photosensitivity, however, limit this therapeutic option. In addition, the immunosuppressive tumor microenvironment has been found to be another critical barrier for the antitumor immunity induced by PDT. Therefore, effectively enhancing the cytotoxicity to tumor cells of low-dose PDT and inhibiting the tumor immunosuppressive tumor microenvironment may be a feasible strategy to overcome these drawbacks of PDT. Here, a sorafenib and chlorin e6 co-loaded reactive oxygen species (ROS)-responsive nanoparticle (NP-sfb/ce6) is developed to improve antitumor responses by intratumoral release of sorafenib at the time of PDT. Under 660-nm laser irradiation, ROS produced by chlorin e6 (ce6) destruct the nanoparticles, resulting in boosted sorafenib cascade release. The rapidly released sorafenib acts synergistically with the low-dose PDT to inhibit tumor growth by inducing strong T cell-dependent local and systemic antitumor immune responses, reprograming the tumor immune microenvironment, and limiting the interaction between cytotoxic CD8+ T cells and immunosuppressive cells. This study provides new avenues for cascade-amplifying antitumor effects of photodynamic therapy.

Semiconducting polymer-based nanoparticles with strong absorbance in NIR-II window for in vivo photothermal therapy and photoacoustic imaging.

Near-infrared (NIR) light-induced photothermal therapy (PTT) has attracted much interest in recent years. In the NIR region, tissue penetration ability of the second biological near-infrared window (1000-1350 nm) is recognized to be stronger than that of the first window (650-950 nm). However, NIR light absorbers in the second NIR region (NIR-II) have been scant even though various NIR light absorbers in the first NIR region (NIR-I) have been widely explored. In this work, a thieno-isoindigo derivative-based semiconducting polymer, PBTPBF-BT, were formulated into PEGylated nanoparticles. The obtained nanoparticle NPPBTPBF-BT exhibited strong absorption in NIR-II region, inherent high photothermal conversion efficacy, and excellent photostability. The in vitro and in vivo PTT study employing 1064 nm laser in NIR-II window revealed that NPPBTPBF-BT could efficiently ablate tumor cell at a power density of 0.42 W/cm2 (the skin tolerance threshold value). Moreover, NPPBTPBF-BT with excellent photostability exhibited enhanced photoacoustic (PA) imaging of tumor in living mice, suggesting the great probability of using NPPBTPBF-BT for in vivo PA imaging-guided PTT in the NIR-II window.