Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma and .

Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX).

Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment.

Regardless of recent progress, melanoma is very difficult to treat, mainly due to the drug resistance modulated by tumor cells as well as by the tumor microenvironment (TME). Among the immune cells recruited at the tumor site, tumor associated macrophages (TAMs) are the most abundant, promoting important tumorigenic processes: angiogenesis, inflammation and invasiveness. Furthermore, it has been shown that TAMs are involved in mediating the drug resistance of melanoma cells.

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5-fluorouracil in vivo.

5-Fluorouracil-based therapy remains the main approach in colorectal cancer, even though there are still some drawbacks, such as chemoresistance. In this study we combined 5-fluorouracil encapsulated in long-circulating liposomes with simvastatin, also encapsulated in long-circulating liposomes, that was previously proved to exert antitumor actions on the same tumor model. The production of angiogenic/inflammatory proteins was assessed by protein array and the production of markers for tumor aggressiveness (Bcl-2, Bax, and nuclear factor [NF]-κB) were determined by western blot analysis.

Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin.

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v.

The prednisolone phosphate‑induced suppression of the angiogenic function of tumor‑associated macrophages enhances the antitumor effects of doxorubicin on B16.F10 murine melanoma cells in vitro.

Several lines of evidence have clearly demonstrated the role of the tumor microenvironment in favoring the drug resistance of melanoma cells, as well as the progression of this cancer type. Since our previous studies proved that the accumulation of prednisolone disodium phosphate (PLP) in melanoma tissue inhibited tumor growth by exerting anti‑angiogenic effects on the most abundant cells of the tumor microenvironment, tumor‑associated macrophages (TAMs), the present study investigated whether PLP could enhance the cytotoxic effects of doxorubicin (DOX) on B16.F10 murine melanoma cells.

Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment.

Our recent studies have demonstrated that the antitumor efficacy of doxorubicin (DOX), administered in long-circulating liposomes (LCL), could be considerably improved after its co-encapsulation with curcumin (CURC). Thus, the question addressed within this article is whether LCL-CURC-DOX can be exploited more efficiently than liposomal DOX for future colorectal cancer therapy. Therefore, we investigated the physicochemical and biological properties of LCL-CURC-DOX and the mechanisms of its antitumor activity in C26 murine colon carcinoma in vivo.

Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells.

Background: Emerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26).

Methods: The cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected.

Double Targeting of C26 Colon Carcinoma Cells and Microenvironmental Protumor Processes Using Liposomal Simvastatin.

Besides cholesterol lowering effects, simvastatin (SIM) at very high doses possesses antitumor actions. Moreover our previous studies demonstrated that tumor-targeted delivery of SIM by using long-circulating liposomes (LCL) improved the therapeutic index of this drug in murine melanoma-bearing mice. To evaluate whether this finding can be exploited for future therapy of colorectal cancer the antitumor activity and the underlying mechanisms of long-circulating liposomal simvastatin (LCL-SIM) efficacy for inhibition of C26 murine colon carcinoma growth were investigated.

HIF-1α acts as a molecular target for simvastatin cytotoxicity in B16.F10 melanoma cells cultured under chemically induced hypoxia.

Our previous studies reported that one of the main mechanisms of the antitumor activity of simvastatin (SIM) in B16.F10 murine melanoma cells was associated with strong suppression of the constitutive cell production of the α subunit of the heterodimeric transcription factor hypoxia-inducible factor (HIF)-1. Thus, the present study aimed to broaden this finding under hypoxic conditions induced by incubation of B16.