Transferrin modified ruthenium nanoparticles with good biocompatibility for photothermal tumor therapy.

In the past two decades, there were various kinds of photothermal agents being synthesised and investigated for their photothermal effect in antitumor applications. However, it is barely reported that the photothermal effect of Ruthenium (Ru) nanoparticles was researched in depth. In this work, we introduced Ru nanoparticles which possess excellent biocompatibility and metabolize easily to the photothermal therapy field. In addition, to improve the cells capacity of absorbing Ru nanoparticles, these Ru nanoparticles were modified by transferrin (Tf-RuNPs). Subsequently, as is expected, the RuNPs exhibit a remarkably integrated and high-quality photothermal property. On the other hand, it is significantly that Tf modification could also strengthen the cells absorptive ability to uptake Ru nanoparticles through endocytosis., Furthermore, both the in vitro cell ablation and in vivo tumor treatment verified that the Tf-RuNPs became ideal photothermal agents for photothermal tumor ablation therapy owing to their low toxicity and high cell destruction capability.

Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C16-SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C16-CC-CS-mPEG) was developed in a similar fashion to that used to yield C16-CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C16-SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C16-SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C16-SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C16-SS-CS-mPEG@Cur. Hence, C16-SS-CS-mPEG@Cur micelles can be useful in tumor therapy.

Redox-responsive mesoporous selenium delivery of doxorubicin targets MCF-7 cells and synergistically enhances its anti-tumor activity.

To reduce the side effects and enhance the anti-tumor activities of anticancer drugs in the clinic, the use of nano mesoporous materials, with mesoporous silica (MSN) being the best-studied, has become an effective method of drug delivery. In this study, we successfully synthesized mesoporous selenium (MSe) nanoparticles and first introduced them to the field of drug delivery. Loading MSe with doxorubicin (DOX) is mainly driven by the physical adsorption mechanism of the mesopores, and our results demonstrated that MSe could synergistically enhance the antitumor activity of DOX. Coating the surface of MSe@DOX with Human serum albumin (HSA) generated a unique redox-responsive nanoparticle (HSA-MSe@DOX) that demonstrated glutathione-dependent drug release, increased tumor-targeting effects and enhanced cellular uptake throug nanoparticle interact with SPARC in MCF-7 cells. In vitro, HSA-MSe@DOX prominently induced cancer cell toxicity by synergistically enhancing the effects of MSe and DOX. Moreover, HSA-MSe@DOX possessed tumor-targeting abilities in tumor-bearing nude mice and not only decreased the side effects associated with DOX, but also enhanced its antitumor activity. Therefore, HSA-MSe@DOX is a promising new drug that warrants further evaluation in the treatments of tumors. STATEMENT OF SIGNIFICANCE: To reduce the side effects and enhance the anti-tumor activities of anticancer drugs, we successfully synthesized mesoporous selenium (MSe) nanoparticles and first introduced them to the field of drug delivery. Loading MSe with doxorubicin (DOX) is mainly driven by the physical adsorption mechanism of the mesopores. Coating the surface of MSe@DOX with Human serum albumin (HSA) generated a unique redox-responsive nanoparticle (HSA-MSe@DOX) that demonstrated glutathione-dependent drug release, increased tumor-targeting effects and enhanced cellular uptake throug nanoparticle interact with SPARC in MCF-7 cells. In vitro and in vivo, HSA-MSe@DOX possessed tumor-targeting abilities and not only decreased the side effects associated with DOX, but also enhanced its antitumor activity. Therefore, HSA-MSe@DOX is a promising new drug that warrants further evaluation in the treatments of tumors.

A redox-responsive strategy using mesoporous silica nanoparticles for co-delivery of siRNA and doxorubicin.

Co-delivery of gene and drug therapies for cancer treatment remains a major goal of nanocarrier research. In this study, mesoporous silica nanoparticles (MSNs) were used to co-deliver siRNA and doxorubicin (Dox) for redox-controlled release. The present nanocarrier (MSNs-SS-siRNA@Dox) has mesoporous silica cores that can be loaded with Dox, while siRNA connects to the core surface by disulfide linkage and plays a gatekeeper role. Disulfide linkages were also utilized to target intracellular GSH, and their cleavage led to the release of Dox and siRNA. Release of siRNA and Dox was correlated with GSH concentrations, and rapid release at 10 mM GSH reflected reductive cleavage of intermediate disulfide linkages. Subsequent experiments using an in vitro Dox delivery and release assay indicated that MSNs-SS-siRNA@Dox significantly enhanced the accumulation of Dox in cells compared with that after treatment with free Dox. Moreover, MSNs-SS-siRNA@Dox has sufficient efficiency to knock down target protein expression. More importantly, MSNs-SS-siRNA@Dox displayed great potential for tumor targeting and achieved satisfactory therapeutic effects on tumor growth inhibition in vivo. In summary, the present nanoparticles may provide an effective strategy for the design and development of controlled release and co-delivery of siRNA and drugs for cancer therapy.

PEG modified graphene oxide loaded with EALYLV peptides for inhibiting the aggregation of hIAPP associated with type-2 diabetes.

Human islet amyloid polypeptide (hIAPP) was found as amyloid aggregate deposits in the pancreatic islets of patients with type-2 diabetes and studies showed that insulin and its derivatives were the potent inhibitors of hIAPP aggregation. However, several emerging therapies with this goal showed limited success due to the instability and inefficiency of insulin derivatives. Nanosized graphene oxide (nGO) possesses high stability and affinity toward aromatic rings. In this study, an insulin-derived peptide, EALYLV, was stabilized by loading on nGO@PEG to inhibit aggregation and hIAPP-induced cytotoxicity. The results showed that nGO@PEG@EALYLV (abbreviated as nGO@PEG@E) can effectively inhibit the aggregation of hIAPP via electrostatic adsorption and specific binding to the active sites of hIAPP. We further evaluated the protective effect of nGO@PEG@E on INS-1 cells in the presence of hIAPP. Treatment with nGO@PEG@E could significantly elevate the viability of INS-1 cells, decrease the level of intracellular reactive oxygen species, and stabilize mitochondrial membrane potential. All the results indicated that nGO@PEG@E could inhibit the aggregation of hIAPP, which reduces its cytotoxicity.

Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance.

Multidrug resistance (MDR) is a major barrier against effective cancer treatment. Dual-delivering a therapeutic small interfering RNA (siRNA) and chemotherapeutic agents has been developed to reverse drug resistance in tumor cells. In this study, amine-terminated generation 5 polyamidoamine (PAMAM) dendrimers (G5.NH2)-modified selenium nanoparticles (G5@Se NP) were synthesized for the systemic dual-delivery of mdr1 siRNA and cisplatin (cis-diamminedichloroplatinum-(II), DDP), which was demonstrated to enhance siRNA loading, releasing efficiency and gene-silencing efficacy. When the mdr1 siRNA was conjugated with G5@Se NP via electrostatic interaction, a significant down-regulation of P-glycoprotein and multidrug resistance-associated protein expression was observed; G5@Se-DDP-siRNA arrested A549/DDP cells at G1 phase and led to enhanced cytotoxicity in A549/DDP cells through induction of apoptosis involving the AKT and ERK signaling pathways. Interestingly, G5@Se-DDP NP were much less reactive than DDP in the reactions with both MT and GSH, indicating that loading of DDP in a nano-delivery system could effectively prevent cell detoxification. Furthermore, animal studies demonstrated that the new delivery system of G5@Se-DDP-siRNA significantly enhanced the anti-tumor effect on tumor-bearing nude mice, with no appreciable abnormality in the major organs. These results suggest that G5@Se NP could be a potential platform to combine chemotherapy and gene therapy technology in the treatment of human disease.

The use of pH-sensitive functional selenium nanoparticles shows enhanced in vivo VEGF-siRNA silencing and fluorescence imaging.

The utility of small interfering RNAs (siRNAs) has shown great promise in treating a variety of diseases including many types of cancer. While their ability to silence a wide range of target genes underlies their effectiveness, the application of therapies remains hindered by a lack of an effective delivery system. In this study, we sought to develop an siRNA-delivery system for VEGF, a known signaling molecule involved in cancer, that consists of two selenium nanoparticles SeNPs and G2/PAH-Cit/SeNPs. A G2/PAH-Cit/SeNP is a pH-sensitive delivery system that is capable of enhancing siRNA loading, thus increasing siRNA release efficiency and subsequent target gene silencing both in vitro and in vivo. In vivo experiments using G2/PAH-Cit/SeNPs@siRNA led to significantly higher accumulation of siRNA within the tumor itself, VEGF gene silencing, and reduced angiogenesis in the tumor. Furthermore, the G2/PAH-Cit/SeNP delivery system not only enhanced anti-tumor effects on tumor-bearing nude mice as compared to SeNPs@siRNA, but also resulted in weak occurrence of lesions in major target organs. In sum, this study provides a new class of siRNA delivery system, thereby providing an alternative therapeutic route for cancer treatment.