HER2 siRNA Facilitated Gene Silencing Coupled with Doxorubicin Delivery: A Dual Responsive Nanoplatform Abrogates Breast Cancer.

The present study investigated the concurrent delivery of antineoplastic drug, doxorubicin, and HER2 siRNA through a targeted theranostic metallic gold nanoparticle designed using polysaccharide, PSP001. The as-synthesized HsiRNA@PGD NPs were characterized in terms of structural, functional, physicochemical, and biological properties. HsiRNA@PGD NPs exposed adequate hydrodynamic size, considerable ζ potential, and excellent drug/siRNA loading and encapsulation efficiency. Meticulous exploration of the biocompatible dual-targeted nanoconjugate exhibited an appealing biocompatibility and pH-sensitive cargo release kinetics, indicating its safety for use in clinics. HsiRNA@PGD NPs deciphered competent cancer cell internalization, enhanced cytotoxicity mediated via the induction of apoptosis, and excellent downregulation of the overexpressing target HER2 gene. Further in vivo explorations in the SKBR3 xenograft breast tumor model revealed the appealing tumor reduction properties, selective accumulation in the tumor site followed by significant suppression of the HER2 gene which contributed to the exclusive abrogation of breast tumor mass by the HsiRNA@PGD NPs. Compared to free drugs or the monotherapy constructs, the dual delivery approach produced a synergistic suppression of breast tumors both in vitro and in vivo. Hence the drawings from these findings implicate that the as-synthesized HsiRNA@PGD NPs could offer a promising platform for chemo-RNAi combinational breast cancer therapy.

Electrospun polysaccharide scaffolds: wound healing and stem cell differentiation.

Irrespective of the labyrinth of fastidiously woven artificial scaffolds, the lack of biocompatibility hampers effective clinical translation, which is the definitive purpose of any biomedical system or device. Hence, the current exploration deals with the fabrication of scaffolds with enhanced bioactivities for wound healing. The methodology used for the fabrication of the scaffolds was electrospinning of the polysaccharide, which is isolated from tamarind seed kernel using the electrospinning process. To improve the antimicrobial activity of the scaffolds, in-house synthesized silver nanoparticles were added to the scaffolds. Wound healing and antimicrobial efficiency of the scaffolds were established in murine models. An insight into the wound healing mechanism was also analyzed using differentiation screening of stem cells grown on scaffolds. The results showed that newly synthesized scaffolds presented excellent wound healing ability along with antimicrobial activity. Furthermore, detailed toxicological evaluations through the histopathology and collagen staining wound sections, the probability of any off-target effects were also ruled out. Differentiation screening showed that adipogenesis was more prominent in cells attached to the scaffolds and markers of adipogenesis were strongly expressed in fluorescent microscopy. Thus we hope that the scaffolds mediate stem cell differentiation in wounds and promote a progressive healing response. Results thus obtained were encouraging and further studies need to embark on to establish the combined role in all aspects studied here.

The inhibitory effect of anti- tumor polysaccharide from Punica granatum on metastasis.

Galactomannan (PSP001) isolated from the fruit rind of Punica granatum was demonstrated as an excellent antioxidant, immunomodulatory and anticancer agent both in vitro and in vivo models. Since the most lethal and debilitating attribute of cancer cells is their ability to evolve to a state of malignancy, with key features like increased angiogenesis, invasion, migration, colony formation, and metastasis, the present study focused on evaluating the effects of the galactomannan on tumor and malignancy. PSP001 effectively reduced the neovascularization in chick embryos highlighting its potential as an angiogenic inhibitor. Furthermore, the invasion, migration and clonogenic capacity of human and murine cancer cells were dramatically inhibited by PSP001. Evaluation of the molecular mechanism of its unique potential revealed the down regulation of key players including VEGF, MMP-2, and MMP-9 with marked elevation of TIMP-1 and TIMP-2. The anti-metastatic potential of PSP001 tested in pulmonary metastasis C57BL/6 mice model deciphered the combinatorial administration with vincristine deliberated better survival rates and decreased metastatic index. The angiogenic inhibition potential of PSP001 was further proved with peritoneal angiogenesis assay in BALB/c mice ascitic tumor model. The outcomes of the current investigation highlight the mode of action of antitumor galactomannan in the reduction of tumor malignancy.