Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles

Abstract

Oxaliplatin is one of the chemotherapeutic agents in the first line therapy for treatment of colorectal cancer. But, limitations of chemotherapy affects the clinical applicability of oxaliplatin depriving its activity at targeted site attributed to the lack of site specificity. This limitation paves the way for undesirable toxic effects to healthy cells resulting in sub-standard drug amount at the tumors obliging for increased dose. The present study emphasizes on formulating gold nanoparticles encapsulating oxaliplatin and later conjugating with anti-DR5 antibody for improved anti-cancer activity in a synergistic and site-specific manner. Oxaliplatin immuno-nanoparticles (Co-Ox-AuNPs) had shown sustained release and confirmed by fluorescence and flow cytometry studies. MTT assay exhibited 3-fold decrease in cell viability of nanoparticles comparable to oxaliplatin. Triple fluorescence method employed in HCT 116 and MCF-7 cells justified its site specificity. Annexin-propidium iodide (PI) and Acridine orangeethidium bromide assays further supported the apoptotic activity. Moreover, caspasedependent molecular mechanism behind oxaliplatin induced anti-cancer activity was explored by western blot analysis. Reduction in tumor size and volume in xenograft tumor models justified its in vitro activity. Oxaliplatin side effects were analyzed in mice and were confirmed for their clinical efficacy highlighting our formulation as an alternative to chemotherapy.

PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect

“…All harmful procedures result in an apoptosis of cancer cells . Because of these unique properties, oxaliplatin is becoming the promising candidate for chemotherapy in the cancer treatment . However, the adverse reactions of oxaliplatin still remain.…”

Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer

“…OXA is a third-generation platinum drug, which inhibits DNA replication [46]. However, the obtained efficacy is suboptimal due to the aggressive side effects OXA and drug resistance of cancer cells [46][47][48]. The pro-apoptotic activities of NPs and OXA were analyzed by flow cytometry for both CT-26 and nontumor cells.…”

Nanocarrier based approaches for targeting breast cancer stem cells

“…Nanocarriers offer various advantages for targeting tumours by overcoming the bioavailability issued of chemotherapeutic agents [24]. They can passively accumulate at the tumour site owing to the leaky vasculature of tumour [25].…”

“…Deregulation of apoptosis and anti-apoptotic (survival) signalling pathways is a characteristic of cancer and a critical determinant of efficacy of chemotherapy [62]. The B-cell lymphoma2 (Bcl2), FLICE like inhibitory protein (cFLIP), nuclear factor-j-B (NFjB), phosphatase and tensin homolog (PTEN), mammalian target of rapamycin(m-TOR), death receptors (DR)-4/5 proteins are the well-characterized regulators for induction apoptosis in BCSCs [21,24,63]. Nanocarrier mediated induction of apoptosis by downregulation of antiapoptotic proteins or upregulation of apoptotic proteins specifically in BCSCs using nanocarriers is an attractive strategy.…”