Novel Polymeric Hybrid Nanocarrier for Curcumin and Survivin shRNA Co-delivery Augments Tumor Penetration and Promotes Synergistic Tumor Suppression

Abstract

A major barrier for co-delivery of gene medicine with small molecular chemotherapeutic drugs in solid tumors is the inadequate tumor penetration and transfection. In this study, a novel polymeric nanocarrier with integrated properties of tumor penetration, nuclear targeting, and pH-responsive features was designed, and further used to achieve the synergistic anti-tumor effect of curcumin (CUR) and survivin shRNA (pSUR). The polymeric hybrid nanocarrier was constructed from the FDA-approved polymer PLGA and a novel conjugated triblock polymer W5R4K-PEG 2K -PHIS (WPH). CUR and pSUR were simultaneously encapsulated in the dual-drug-loaded nanoparticles (CUR/pSUR-NPs) by a modified double-emulsion solvent evaporation (W/O/W) method. The obtained nanoparticles exhibited better pharmaceutical properties with a uniform spherical morphology and sustained release manners of CUR and pSUR. Excellent features including preferable cellular uptake, efficient endosomal escape, enhanced tumor penetration, and elevated transfection efficiency were further proven. Additionally, a markedly enhanced anti-tumor efficacy for CUR/shRNA-NPs was achieved on SKOV-3 and Hela cells. The synergistic anti-tumor effect involved the inhibition of tumor cell proliferation, induction of cell apoptosis, and the activation of caspase-3 pathways. This work sets up an innovative co-delivery nanosystem to suppress tumor growth, contributing to the development of a comprehensive nanoparticulate strategy for future clinical applications.

Oral Codelivery of WR-1065 Using Curcumin-Linked ROS-Sensitive Nanoparticles for Synergistic Radioprotection

“…WR-1065-loaded NPs were constructed using a modified double emulsification technique (W/O/W) as previously reported. , The operation process is as follows. First, free WR-1065 (150 mg) was dissolved in 0.3 mL of pure water as an internal aqueous phase (W 1 ).…”

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer

“…Multiple layers of lipids, polymers, and organic–inorganic compounds may protect the core materials, along with the solubility and permeability modifications of the entrapped active ingredients [ 370 ]. Recently, curcumin and survivin shRNA loaded in polymeric hybrid NPs with PLGA-conjugated triblock polymers (W5R4K-PEG2K-PHIS) showed better penetration into the TME and synergistic tumor suppression action [ 371 ].…”

Combined Nanochemotherapy Using Doxorubicin and Curcumin as an Example

“…In other cases, it is necessary to have polymers that capture, solubilize and control the release of the drug without resorting to chemical conjugation [36], such as Pluronic® micelles [34,41,42], poly(lactic acid) (PLG ), poly(lactic co-glycolic acid) (PLGA) [43], chitin [44,45], chitosan [34,35,42]. For example, a multifunctional co-delivery system that coencapsulates hydrophobic chemotherapeutic drugs (curcumin) and hydrophilic therapeutic drugs (Survivin shRNA genes) in polymer nanoparticles (PLGA polymer and conjugated triblock polymer) is a promising strategy for clinical application in cancer therapy [46]. Co-delivery of curcumin and Survivin shRNA increases tumor penetration and promotes synergistic inhibition (suppression) of SKOV-3 and Hela cells.…”

“…Co-delivery of curcumin and Survivin shRNA increases tumor penetration and promotes synergistic inhibition (suppression) of SKOV-3 and Hela cells. The synergistic antitumor effect includes inhibition of tumor cell proliferation, induction of cell apoptosis, and activation of caspase-3 pathways [46]. For some drugs, it is desirable to have a high degree of homogeneity, which gives predictable conformations in solution and increased ability to load drugs [36].…”