Tumor Microenvironment Responsive Drug‐Dye‐Peptide Nanoassembly for Enhanced Tumor‐Targeting, Penetration, and Photo‐Chemo‐Immunotherapy

Abstract

Nanomedicine constructed by therapeutics has unique and irreplaceable advantages in biomedical applications, especially in drug delivery for cancer therapy. The strategy, however, used to construct the therapeutics-based nanomedicines with tumor microenvironmental factor responsiveness is still sophisticated. In this study, an easy-operating procedure is used to construct a therapeutics-based nanosystem with active tumor-targeting, enhanced penetration, and stimuli-responsive drug release behavior as well as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) blockading mediated immunomodulation to enhance tumor immunotherapy. The matrix metalloproteinase-2 responsive peptide with the existence of Lyp-1 sequence contributes to the success of active tumor-targeting and the enhancement of the penetration of the nanoparticles in tumor tissue. The obtained nanosystem strikingly inhibits the primary tumor growth in the first 24 h (more than 97.5% of tumor cells are inhibited), and total inhibition can be achieved with the combination of photothermal therapy. IR820, which is served as the carrier for the therapeutics, is used as a photosensitizer for photothermal therapy. The progress and aggression of distal tumor has further been alleviated by a d-peptide which is an antagonist for PD-1/PD-L1 blockage. Therefore, a therapeutics-constructed multifunctional nanosystem is provided to realize a combinational therapeutic strategy to enhance the therapeutic outcome.

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

“…For instance, the tumor-homing peptide LyP-1, which was reported to bind preciously with p32 protein of a series of tumor cells, could be conjugated with nanoparticles to realize enhanced tumor targeting. Furthermore, improved therapeutic outcomes resulting from treatment with these modified nanoparticles were achieved by photo-thermotherapy, photo-chemotherapy and photo-immunotherapy in our previous work [62][63][64]. In addition to LyP-1, the RGD peptide, a tripeptide consisting of L-arginine, glycine and L-aspartic acid, is a cell adhesion sequence that mimics cell adhesion proteins and can bind to integrin receptors on angiogenic endothelial cells and tumor cells, such as malignant glioblastoma cells, bladder cancer cells and α V β 3 integrin receptor-overexpressing breast cancer cells [65].…”

Advanced biomaterials for cancer immunotherapy

“…Different biomaterials use various means and technologies to play an important role in cancer prevention [34][35][36][37][38]. To achieve precise antitumor effects, these advanced biomaterials with different functions can be used to deliver immunopharmaceuticals to organs or tissues (such as the mucosa or skin) that are rich in immune cells by different routes of administration (for instance, intranasally [39], orally [40], and subcutaneously [41]).…”

<p>Nanomaterial-Based Tumor Photothermal Immunotherapy</p>

“…International Journal of Nanomedicine 2020:15 9170 cells and had no new tumor formation after 60 days, suggesting that the photothermal immunotherapy effectively induced long-term immunity to MB49 cells. Peng et al 183 used NIR dyes (IR820) chemotherapy drugs (docetaxel, DTX) to prepare nanoparticles with high drug-loading rates. In addition, a 27 amino acid polypeptide (named CF27) containing 12 units of amino acid PD-L1 agonist was introduced that could block the immune checkpoint PD-1/PD-L1 and self-crosslinking of drug-loading nanoparticles.…”