Selected Research Publications

Materials-based antigen delivery systems can augment the immune response by improving antigen uptake in antigen-presenting cells, targeting lymph nodes, prolonging antigen exposure, and enhancing cross-presentation. Here, a vaccine delivery platform constructed by one-step in situ polymerization is reported, weaving a biodegradable polymer network around the antigen surface. An antigen nanocapsule (NC7) capable of inducing dendritic cell activation and cross-presentation is identified. Further mechanistic studies revealed that NC7 activated the cGAS-STING pathway in a cGAS-dependent manner. Moreover, the subcutaneously injected NC7 accumulated in the lymph nodes and elicited strong cytotoxic T cell immunity and T cell memory against established cancer. Collectively, the immunomodulatory effect of cationic antigen carriers, enabling potential application in cancer vaccines, is uncovered.

Both targeting and penetrating ability are the key characteristics for tissue probing and precise delivery. To construct an efficient nano probing and delivery system toward human epidermal growth factor receptor 2 (HER2) positive cancer, we established a nano liposomal system functionalized with a newly screened HER2 targeting peptide (HP2, YDLKPEPH) and the cell-penetrating peptide TAT simultaneously. Compared with the monofunctionalized liposomal probes, the dual-functional ones demonstrated a synergic effect in cell uptake, drug delivery, and in vivo imaging. The improved efficacy of the synergistic system provides a prospective strategy for cancer diagnosis and therapy.

Biopharmaceuticals, including proteins, DNAs, and RNAs, hold vast promise for the treatment of many disorders, such as cancer, diabetes, autoimmune diseases, infectious diseases, and rare diseases. The application of biopharmaceuticals, however, is limited by their poor stability, immunogenicity, suboptimal pharmacokinetic performance, undesired tissue distribution, and low penetration through biological barriers. In situ polymerization provides an appealing and promising platform to improve the pharmacological characteristics of biopharmaceuticals. Instead of the traditional grafting-to polymer–biomolecule conjugation, in situ polymerization grows polymers on the surfaces of the biomacromolecules, resulting in easier purification procedures, high conjugation yields, and unique structures. Herein, this review surveys recent advances in the polymerization methodologies. Additionally, we further review improved therapeutic performance of the resultant nanomedicines. Finally, the opportunities, as well as the challenges, of these nanocomposites in the biomedical fields are discussed.

Aminopeptidase N (APN/CD13) is closely related to the growth of cancers and is suggested as a suitable target for anti-cancer therapy. Based on the one-bead-one-compound (OBOC) approach on a microarray device, we screened out a novel affinity peptide LN (YEVGHRC). It was determined that LN could specifically recognize and bind to APN. Moreover, LN-functionalized liposomes (LN-LS) could achieve efficient nano-encapsulated drug delivery under APN-overexpressing tumor conditions in vitro and in vivo. We expect that LN-LS could provide a new strategy for APN-positive tumor diagnosis and therapy.

One switchable nanodelivery system was constructed. Liposomes were functionalized by a novel dual-recognition peptide STP, which is pH-responsive as well as the affinity ligand of tumor marker VEGFR2 (the angiogenesis marker vascular endothelial growth factor receptor 2). Efficient drug delivery and in vivo therapy could be turned on and accelerated only in the conditions of VEGFR2 overexpression and a mild acidic environment. We envisioned that the successful demonstration of this switchable nanocarrier system would open a new avenue on rapid cytoplasmic delivery for specific cancer diagnostics and therapeutics.

We present here a specific targeting nanocarrier system by functionalization of liposomes with one new type of breast cancer targeting peptide (H6, YLFFVFER) by a micromixer with high efficiency. Antitumor drugs could be successfully delivered into human epidermal growth factor receptor 2 (HER2) positive breast cancer cells with high efficiency in both in vivo and ex vivo models.