ArticleInternational journal of nanomedicine2013
Codelivery of zoledronic acid and doublestranded RNA from core-shell nanoparticles.
Article in International journal of nanomedicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 19 citations in OpenAlex.
- Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles.Bioengineering & translational medicine · 2021Review
- Functionalized Selenium Nanotherapeutics Synergizes With Zoledronic Acid to Suppress Prostate Cancer Cell Growth Through Induction of Mitochondria-Mediated Apoptosis and Cell Cycle S Phase Arrest.Frontiers in oncology · 2021Article
- The Antitumor Effect of Lipophilic Bisphosphonate BPH1222 in Melanoma Models: The Role of the PI3K/Akt Pathway and the Small G Protein Rheb.International journal of molecular sciences · 2019Article
- Development of Drugs Based on High-Polymeric Double-Stranded RNA for Antiviral and Antitumor Therapy.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2019Article
- Reverse Microemulsion-Based Synthesis of (Bis)phosphonate-Metal Materials with Controllable Physical Properties: An Example Using Zoledronic Acid-Calcium Complexes.ACS applied materials & interfaces · 2017Article
- Toward RNA nanoparticle vaccines: synergizing RNA and inorganic nanoparticles to achieve immunopotentiation.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2017Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundZoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acid-polycytidylic acid [poly (I:C)] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly.
methodsCationic lipid-coated calcium phosphate nanoparticles (LCP) were developed to enable intracellular codelivery of zoledronic acid and poly (I:C). LCP codelivering zoledronic acid and poly (I:C) were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C) and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice.
resultsLCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17) and high zoledronic acid encapsulation efficiency (94%) were achieved. LCP loaded with zoledronic acid and poly (I:C) had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P < 0.05). Furthermore, codelivery of zoledronic acid and poly (I:C) by LCP had higher cytotoxicity than delivering poly (I:C) alone by LCP (P < 0.05), indicating a synergism between zoledronic acid and poly (I:C). Finally, the antitumor study in melanoma-bearing mice also demonstrated synergism between zoledronic acid and poly (I:C) codelivered by LCP.
conclusionCationic lipid-coated calcium phosphate nanoparticles constructed for codelivery of zoledronic acid and double-stranded RNA poly (I:C) had better antitumor activity both in vitro and in vivo. Future preclinical development of LCP encapsulating zoledronic acid and poly (I:C) for the treatment of human cancer is under way.
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