iRGD Tumor-Penetrating Peptide-Modified Nano-Delivery System Based on a Marine Sulfated Polysaccharide for Enhanced Anti-Tumor Efficiency Against Breast Cancer

Abstract

Background: Breast cancer is a common malignancy in women. Conventional clinical therapies for breast cancer all display moderate clinical efficacies and limitations. It is urgent to explore the novel and combined therapeutic strategies for breast cancer to meet clinical demand. Methods: An iRGD tumor-penetrating peptide-modified nano-delivery system (denoted as iRGD-PSS@PBAE@JQ1/ORI nanoparticles) based on a marine sulfated polysaccharide was developed by codelivery of JQ1 (BET inhibitor) and oridonin (ORI, bioactive diterpenoid derived from traditional Chinese medicine herb). The iRGD-PSS@PBAE@JQ1/ORI NPs, surface modified with iRGD peptide conjugated propylene glycol alginate sodium sulfate (iRGD-PSS). The antitumor efficacy was evaluated both in vitro and in vivo. Results:The prepared iRGD-PSS@PBAE@JQ1/ORI NPs effectively enhanced the tumor targeting and cellular internalization of JQ1 and ORI. Thus, JQ1 exerted the reversal effect on immune tolerance by decreasing the expression of PD-L1, while ORI displayed multiple antitumor effects, such as antiproliferation, inhibition of intracellular ROS production and inhibition of lactic acid secretion. Conclusion: Our data revealed that iRGD peptide could significantly improve the cellular internalization and tumor penetration of the nano-delivery system. The combination of JQ1 and ORI could exert synergistic antitumor activities. Taken together, this study provides a multifunctional nanotherapeutic system to enhance the anti-tumor efficiency against breast cancer.

Advances in nanomaterial-based targeted drug delivery systems

“…As a peptide with tumor penetrating activity, iRGD (CRGDK/RGPD/EC) can be used for the surface modification of nanoparticles. Many experimental studies on iRGD have confirmed that its modification in iRGD can improve the targeting and retention of nanoparticles in tumors (Lin et al, 2020;Chen B. et al, 2022). Immune cells in the tumor microenvironment (TME) also influence the aggregation of nanoparticles.…”

Emerging Epigenetic‐Based Nanotechnology for Cancer Therapy: Modulating the Tumor Microenvironment

“…The iRGD-PSS@PBAE@JQ1/ORI NPs effectively enhanced tumor targeting due to the tumor-overexpressed 𝛼v𝛽3 integrin receptors; JQ1 and ORI were released from nanoparticles in response to intracellular pH/GSH and achieved remarkable synergistic anti-breast cancer efficiency by reversing PD-L1-mediated immune tolerance, increasing intracellular ROS production, and inhibiting lactic acid secretion. [111] Malignant tumors are usually associated with overexpression of HDAC. A novel nanoplatform (M1-EM-SUCS NPs) was established in which M1 macrophagederived exosome membranes camouflaged mesoporous silicamodified lanthanide-doped upconversion nanoparticles (UCs) loaded with SAHA.…”

“…[124,126] Overexpression of 𝛼v𝛽3 integrin receptors, CD44, and mannose receptors in diverse tumor types (e.g., colorectal cancer, breast cancer, and NSCLC) also provides a potential target for iRGD, HA, or mannose-modified nanoparticulate formulations. [55,95,101,108,111] Furthermore, biomimetic nanoparticles including cell membrane-camouflaged nanoparticles (e.g., homologous cancer cell membranes and PD1-expressing T lymphocyte membrane), [94,102,114,116,117,123] exosome-disguised nanoparticles (e.g., M1-derived exosome), [112] albumin nanoparticles, [114] and lactoferrin nanoparticles, [55] served as novel nanotechnology for targeting tumor cells and regulating the TME in the treatment of breast cancer, colorectal cancer, glioma, melanoma, and lung cancer.…”

Personalized Targeted Therapeutic Strategies against Oral Squamous Cell Carcinoma. An Evidence-Based Review of Literature

“…to completely destroy cancer and compensate for the poor efficiency of single receptor targeting. 139 , 140 Therefore, investigating the target receptors provides huge potential in further researches and oncological clinical applications including the field of early detection, prognosis prediction, clinical outcome evaluation, and personalized diagnosis and therapies, 141 while great challenges need to be solved with well-designed therapeutic strategy and further proper randomized clinical trials for personalized OSCC therapy.…”