Reprogramming Hypoxic Tumor-Associated Macrophages by Nanoglycoclusters for Boosted Cancer Immunotherapy.

The tumor-associated macrophages (TAMs) in intratumoral hypoxic regions are key drivers of immune escape. Reprogramming the hypoxic TAMs to antitumor phenotype holds great therapeutic benefits but remains challenging for current drugs. Here, an in situ activated nanoglycocluster is reported to realize effective tumor penetration and potent repolarization of hypoxic TAMs.

A Polyvalent Peptide CD40 Nanoagonist for Targeted Modulation of Dendritic Cells and Amplified Cancer Immunotherapy.

Targeted immunomodulation through biomolecule-based nanostructures, especially to dendritic cells (DCs), holds great promise for effective cancer therapy. However, construction of high-performance agonist by mimicking natural ligand to activate immune cell signaling is a great challenge so far. Here, a peptide-based nanoagonist toward CD40 (PVA-CD40) with preorganized interfacial topological structure that activates lymph node DCs efficiently and persistently, achieving amplified immune therapeutic efficacy is described.

Oncolytic peptide nanomachine circumvents chemo resistance of renal cell carcinoma.

Due to intrinsic and acquired chemo/radiotherapy-resistance, renal cell carcinoma shows limited therapeutic response to clinically utilized targeting drugs. Here a tumor-activated oncolytic peptide nanomachine is devised to selectively lysing tumor cell membrane without causing drug resistance. Specifically, in the acidic tumor microenvironment, the oncolytic peptide nanomachine automatically activated through morphologically transformation from nanoparticles to nanofibrils with restoring α-helical conformation, which physically bind to tumor cell membrane with multiple (spatially correlated and time-resolved) interactions and subsequently lyse local cell membrane.

Nanomedicine enables spatiotemporally regulating macrophage-based cancer immunotherapy.

Cancer immunotherapy, leveraging the host's coordinated immune system to fight against tumor has been clinically validated. However, the modest response owing to the multiple ways of tumor immune evasion is one of the challenges in cancer immunotherapy. Tumor associated macrophages (TAMs), as a major component of the leukocytes infiltrating in all tumors, play crucial roles in driving cancer initiation, progress and metastasis via multiple mechanisms such as mediating chronic inflammation, promoting angiogenesis, taming protective immune responses, and supporting migration and intravasation.