Tumor-targeted Delivery Of Doxorubicin Research Articles

All-Trans Retinoic Acid and Doxorubicin Delivery by Folic Acid Modified Polymeric Micelles for the Modulation of Pin1-Mediated DOX-Induced Breast Cancer Stemness and Metastasis.

Stemness and metastasis are the two main challenges in cancer therapy and are related to disease relapse post-treatment. They both have a strong correlation with chemoresistance and poor prognosis, ultimately leading to treatment failure. It has been reported that chemotherapy can induce stemness and metastasis in many cancer types, especially treatment with the chemotherapeutic agent doxorubicin (DOX) in breast cancer. A combination treatment is an efficient and elegant approach in cancer therapy through simultaneous delivery of two or more drugs with a delivery system for its synergistic effect, which is not an additive of two individual drugs. Herein, we report a combinatorial system with DOX and all-trans retinoic acid (ATRA) to address both of the above issues. As a common critical regulatory factor for oncogenic signal transduction pathways, Pin1 is a specific isomerase highly expressed within various tumor cells. ATRA, a newly identified Pin1 inhibitor, can abolish several oncogenic pathways by effectively inhibiting and degrading overexpressed Pin1. We successfully developed a folic acid (FA)-modified chitosan (CSO)-derived polymer (FA-CSOSA) and obtained FA-CSOSA/DOX and FA-CSOSA/ATRA drug-loaded micelles. FA modification can improve the uptake of the nanoparticles in tumor cells and tumor sites via folate receptor-mediated cell internalization. Compared to treatment with DOX alone, the combined treatment induced 4T1 cell apoptosis in a synergistic manner. Reduced stemness-related protein expression and inhibited metastasis were observed during treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA and were found to be associated with Pin1. Further in vivo experiments showed that treatment with FA-CSOSA/DOX and FA-CSOSA/ATRA resulted in 85.5% tumor inhibition, which was 2.5-fold greater than that of cells treated with DOX·HCl alone. This work presents a new paradigm for addressing chemotherapy-induced side effects via degradation of Pin1 induced by tumor-targeted delivery of DOX and ATRA.

Modularized peptides modified HBc virus-like particles for encapsulation and tumor-targeted delivery of doxorubicin

Virus-mimicking particles have made great contribution to the development of nanomedicine. Herein, several modularized peptides (lipophilic NS5A peptide, 6xHis tag, and tumor-targeting peptide RGD) were genetically inserted into the C-terminus and the major immunodominant loop region (MIR) of hepatitis B core protein (HBc), respectively. This study demonstrated that the recombinant HBc-based VLPs could participate in self-assembly of monodisperse nanoparticles (33.6±3.5nm) with well-defined morphology, and DOX can be packaged into VLNPs without any chemical modification. Moreover, the HBc-based VLPs could specifically target to cancer cells via the interaction with overexpressed integrin αvβ3. The treatment with DOX-loaded HBc-based VLPs showed a significant inhibition of tumor growth (90.7% TGI) and less cardiotoxicity in B16F10 tumor-bearing mice models than that with the free DOX. Importantly, the results may offer an easy way to give a variety of ideal functional modulations for VLPs, thereby extending its potential biomedicine applications.

Acidity-triggered surface charge neutralization and aggregation of functionalized nanoparticles for promoted tumor uptake

A polymeric nanovehicle featured with histidine-rich surface was developed for tumor-targeted delivery of doxorubicin.