Peptide Dendrimer–Doxorubicin Conjugate‐Based Nanoparticles as an Enzyme‐Responsive Drug Delivery System for Cancer Therapy

Abstract

Peptide dendrimers have shown promise as an attractive platform for drug delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive drug delivery vehicle. The drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale drug delivery vehicle for the breast cancer therapy.

Doxorubicin-loaded polysaccharide nanoparticles suppress the growth of murine colorectal carcinoma and inhibit the metastasis of murine mammary carcinoma in rodent models

“…Nevertheless, varying degrees of heart, and liver damages were observed from H&E stained organ slices in all the DOX involved groups. Obvious cardiotoxicity was induced by DOX plus CDDP treated groups due to the observed hyperemia, myocardial fiber breakage with acute inflammatory cell infiltration, critical pathological changes, and necrosis of the muscle fibers in cardiac tissue, which was in consistent with the previous report [43]. In contrast, the treatment of tumor bearing mice by DOX-encapsulated CL-Nanoparticles obviously reduced the blight of heart.…”

RGD peptide-modified multifunctional dendrimer platform for drug encapsulation and targeted inhibition of cancer cells

“…As a consequence, it may be advantageous to use dendrimers as DOX carriers [41]. It has been shown that DOX can be either encapsulated within dendrimers via physical encapsulation/complexation [2,42] or conjugated onto the surface of dendrimers via a covalent linkage [43][44][45][46]. Each method has its own advantages and drawbacks.…”

Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery

“…Within the last decade, persistent efforts have been made in the development of stimuli-responsive drug delivery systems that can, when exposed to external stimuli, produce physicochemical changes that favor drug release at the target site. Depending on the target, typical biological stimuli have been exploited for triggered drug release including temperature [1], pH [2][3][4], magnetic field [5,6], redox potential [7][8][9], enzymes [10][11][12] or two parameters at the same time [13][14][15]. pH controlled release systems are particularly more interesting because we can find physiologically the pH gradients relevant for drug targeting.…”