Cryo-Shocked Tumor-Reprogrammed Sonosensitive Antigen-Presenting Cells Improving Sonoimmunotherapy via T Cells and NK Cells Immunity.

Ultrasound therapy has turned up as a noninvasive multifunctional tool for cancer immunotherapy. However, the insufficient co-stimulating molecules and loss of peptide-major histocompatibility complex I (MHC-I) expression on tumor cells lead to poor therapy of sonoimmunotherapies. Herein, this work develops a sonosensitive system to augment MHC-I unrestricted natural killer (NK) cell-mediated innate immunity and T cell-mediated adaptive immunity by leveraging antigen presentation cell (APC)-like tumor cells.

Spatial-Drug-Laden Protease-Activatable M1 Macrophage System Targets Lung Metastasis and Potentiates Antitumor Immunity.

Lung metastasis is a critical cause of cancer mortality and its therapy is largely challenged by the limited drug delivery efficiency and robust immunosuppression in metastatic tumors. Herein, we designed a spatial-drug-laden M1 macrophage system with liposomal R848 inside and fibroblast activation protein protease (FAP)-sensitive phospholipid-DM4 conjugate on the membrane of M1 macrophage (RDM). RDM could preferentially accumulate at the metastatic lesions in lungs and responsively release the therapeutic agents as free drug molecules or drug-loaded nanovesicles.

Bioinspired nanovehicle of furoxans-oxaliplatin improves tumoral distribution for chemo-radiotherapy.

The spatiotemporal distribution of therapeutic agents in tumors remains an essential challenge of radiation-mediated therapy. Herein, we rationally designed a macrophage microvesicle-inspired nanovehicle of nitric oxide donor-oxaliplatin (FO) conjugate (M-PFO), aiming to promote intratumor permeation and distribution profiles for chemo-radiotherapy. FO was responsively released from M-PFO in intracellular acidic environments, and then be activated by glutathione (GSH) into active oxaliplatin and NO molecules in a programmed manner.

Microvesicle-inspired oxygen-delivering nanosystem potentiates radiotherapy-mediated modulation of tumor stroma and antitumor immunity.

The efficacy of radiotherapy is greatly challenged by intense hypoxia, intricate stroma and suppressive immune microenvironments in tumors. Herein, we rationally designed a microvesicle-inspired oxygen-delivering polyfluorocarbon nanosystem loading DiIC18(5) and halofuginone (M-FDH) with prominent capacity of improving tumor oxygenation and intratumor distribution, synergizing radiation to disrupt tumor stroma and boost antitumor immunity for combinational cancer therapy. M-FDH produced a 10.

ROS-Responsive Nanocomplex of aPD-L1 and Cabazitaxel Improves Intratumor Delivery and Potentiates Radiation-Mediated Antitumor Immunity.

Despite the promising benefits of immune checkpoint inhibitors (ICIs) in clinical cancer treatments, the therapeutic efficacy is largely restricted by low antitumor immunity and limited intratumor delivery in solid tumors. Herein, we designed a reactive oxygen species (ROS)-responsive albumin nanocomplex of antiprogrammed cell death receptor ligand 1 (aPD-L1) and cabazitaxel (RAN-PC), which exhibited prominent tumor accumulation and intratumor permeation in 4T1 tumors. Compared with the negative control, the RAN-PC + radiation treatment (RAN-PC+X) produced a 3.

Poly(maleic anhydride-alt-1-octadecene)-based bioadhesive nanovehicles improve oral bioavailability of poor water-soluble gefitinib.

The poor water solubility and inadequate oral bioavailability of gefitinib (Gef) remain a critical issue to achieve the therapeutic outcomes. Herein, we designed a poly(maleic anhydride-alt-1-octadecene) (PMA/C18) based lipid nanovehicle (PLN) to improve the intestinal absorption and oral bioavailability of poorly water-soluble Gef. PLN was nanometer-sized particles, and Gef was dispersed in the PLN formulation as amorphous or molecular state.

Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR).

Strategies of engineering nanomedicines for tumor retention.

The retention of therapeutic agents in solid tumors at sufficient concentration and duration is crucial for their antitumor effects. Given the important contribution of nanomedicines to oncology, we herein summarized two major strategies of nanomedicines for tumor retention, such as transformation- and interactions-mediated strategies. The transformation-mediated retention strategy was achieved by enlarging particle size of nanomedicines or modulating the morphology into fibrous structures, while the interactions-mediated retention strategy was accomplished by modulating nanomedicines to promote their interactions with versatile cells or components in tumors.

Nanomedicine Strategies to Circumvent Intratumor Extracellular Matrix Barriers for Cancer Therapy.

The dense and heterogeneous physical network of the extracellular matrix (ECM) in tumors represents a formidable barrier that limits intratumor drug delivery and the therapeutic efficacy of many anticancer therapies. Here, the two major nanomedicine strategies to circumvent intratumor ECM barriers: regulating the physiochemical properties of nanomedicines and remodeling the components and structure of the ECM are summarized. Nanomedicines can be rationally regulated by optimizing physiochemical properties or designed with biomimetic features to promote ECM permeation capability.