Engineered CpG-Loaded Nanorobots Drive Autophagy-Mediated Immunity for TLR9-Positive Cancer Therapy.

Smart nanorobots have emerged as novel drug delivery platforms in nanomedicine, potentially improving anti-cancer efficacy and reducing side effects. In this study, an intelligent tumor microenvironment-responsive nanorobot is developed that effectively delivers CpG payloads to Toll-like receptor 9 (TLR9)-positive tumors to induce autophagy-mediated cell death for immunotherapy. The nanorobots are fabricated by co-self-assembly of two amphiphilic triblock polymer peptides: one containing the matrix metallopeptidase 2 (MMP2)-cleaved GPLGVRGS motif to control the mechanical opening of the nanorobots and provide targeting capability for TLR-9-positive tumors and the other consisting of an arginine-rich GRRRDRGRS sequence that can condense nuclear acid payloads through electrostatic interactions.

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.

phase transitional polymeric vaccines for improved immunotherapy.

Cancer vaccines have exhibited immense potential in cancer treatment. Through activating the host's immune system, vaccines stimulate extensive functional T cells to eliminate cancer. However, the therapeutic efficacy of cancer vaccines is limited by their inferior lymph node delivery and inadequate uptake of dendritic cells.

Rationally designed modular drug delivery platform based on intracellular peptide self-assembly.

Modulated molecular design-based intracellular self-assembly strategy has showed great potentiality in drug delivery, due to its assembling nature-resulted optimized drug biodistribution and metabolism. The modular designing concept endows the delivery system multiple functions, such as, selectivity and universality to improve the pharmacokinetics of loaded drugs. However, the accurate controlling of the self-assembling process in desired site to achieve optimal drug delivery is posed great challenges toward rational molecular design.

Conformational Transition-Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy.

Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α-helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep-HCO modified with bicarbonates on guanidine groups is designed.

Therapeutic Vaccines for Cancer Immunotherapy.

The rapid development of nanobiotechnology has enabled progress in therapeutic cancer vaccines. These vaccines stimulate the host innate immune response by tumor antigens followed by a cascading adaptive response against cancer. However, an improved antitumor immune response is still in high demand because of the unsatisfactory clinical performance of the vaccine in tumor inhibition and regression.

Controllable Self-Assembly of Peptide-Cyanine Conjugates In Vivo as Fine-Tunable Theranostics.

The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide-cyanine conjugates that intracellularly self-assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase-3/7 after entering the cells.

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.

Click Reaction-Assisted Peptide Immune Checkpoint Blockade for Solid Tumor Treatment.

One of the major challenges of immune checkpoint blockade (ICB) is the poor penetration of antibody for solid tumor treatment. Herein, peptides with deeper penetration capability are used to develop a click reaction-assisted peptide immune checkpoint blockade (CRICB) strategy that could construct assemblies, enabling enhanced accumulation and prolonged PD-L1 occupancy, ultimately realizing high-performance tumor inhibition. First, the free DBCO-modified targeting peptide (TP) efficiently recognizes and binds PD-L1 in a deep solid tumor.

Manipulation of Dendritic Cells by an Autophagy-Regulative Nanoactivator Enables Effective Cancer Immunotherapy.

Cellular immunotherapeutics aim to employ immune cells as anticancer agents. engineering of dendritic cells (DCs), the initial role of an immune response, benefits tumor elimination by boosting specific antitumor responses. However, directly activating DCs is less efficient and therefore quite challenging.