Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy

Abstract

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

Porphyrin–peptide conjugates in biomedical applications

“…The research on porphyrin–peptide conjugates has been constantly growing and it is expanding also in the nanomedicine field where nanostructures derived by the self‐assembling properties of porphyrin–peptide conjugates can accumulate in the tumor tissue through the enhanced permeability and retention effect, overcoming some limitations of conventional PS formulations . Moreover new biomedical applications are emerging for these nanostructures, such as contrast agents in photoacoustic imaging and photothermal agents in thermal ablation of cancer cells and tumors …”

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

“…Hammer designed two conjugates, cyclic mPeg-CNGRC-Pt and cyclic mPeg-CNGRC-Pten, [85] to obtain a selective killing effect in chemotherapy. [92] Nanoplates formed from anti-EGFR peptide-conjugated triangular gold have been employed for PTT, incorporating the functions of computed tomography and photoacoustic [99] Copyright 2017, American Chemical Society. [86] This conjugate was cleaved by PSA to release TGX-221 for prostate cancer treatment.…”

“…[20,96] Hence, responsive peptides have been further introduced into cancer diagnostic and therapeutic applications. [99] They fabricated a chimeric peptide including the alkylated PpIX and dimethylmaleic anhydride (DMA)-modified peptide with the sequence Ala-Glu-Ala-Glu-Ala-Lys-AlaLys) 2 (AEAEAKAKAEAEAKAK), namely, PEAK-DMA. [98] Using this difference, Han et al designed nanodrugs with alterable geometrical shape that were induced by pH.…”

Non‐viral gene delivery for cancer immunotherapy

“…Recent studies have explored the tumor microenvironment for enhanced therapeutic performance and targeted drug delivery . NP‐based formulations have successfully exploited the unique tumor microenvironment for specific cellular uptake and timely drug release, as well as an effective endosomal release of the therapeutics . Moreover, NP‐based delivery systems can effectively target tumors via enhanced permeability and a retention effect or overexpressing receptors .…”

“…40,41 NP-based formulations have successfully exploited the unique tumor microenvironment for specific cellular uptake and timely drug release, as well as an effective endosomal release of the therapeutics. [42][43][44] Moreover, NP-based delivery systems can effectively target tumors via enhanced permeability and a retention effect or overexpressing receptors. 45 Therefore, the accumulation, permeation and cellular uptake efficiency can be improved greatly by tumor microenvironment-responsive nanovectors.…”