Development of Zoledronic Acid-Based Nanoassemblies for Bone-Targeted Anticancer Therapy

Abstract

Bone metastasis occurs in the majority of cancer patients, which hampers quality of life and significantly decreases survival. Aggressive chemotherapy is a traditional treatment regimen that induces severe systemic toxicities. Therefore, bone-directed therapies are highly warranted. We report a novel nanoparticle formulation that is composed of poly­(vinylpyrrolidone) and tannic acid core nanoparticles (PVT NPs) that forms self-assembly with zoledronic acid (ZA@PVT NPs). The construction of ZA@PVT NPs was confirmed by particle size, zeta potential, transmission electron microscopy, and spectral analyses. An optimized bone-targeted ZA@PVT NPs formulation showed greater binding and internalization in in vitro with metastasis prostate and breast cancer cells. ZA@PVT NPs were able to deliver ZA more efficiently to tumor cells, which inhibited proliferation of human prostate and breast cancer cells. In addition, ZA@PVT NPs were capable of targeting mouse bones and prostate tumor microarray tissues (ex vivo) while sparing all other vital organs. More importantly, ZA@PVT NPs induce chemo sensitization to docetaxel treatment in cancer cells. Overall, the study results confirm that ZA-based, bone-targeted NPs have great potential for the treatment of bone metastasis in the near future.

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

“…Moreover, a targeted delivery strategy shows great potential to solve systemic toxic effects and multidrug resistance, which are longstanding problems with the standard cancer chemotherapy treatment. 142,143 Bone-modifying agents with a high affinity for bone are used for active bone targeting, including alendronate, [144][145][146] zoledronic acid, [147][148][149] aspartic acid, 150 denosumab, 151 and aptamers. 152,153 Nanomaterials and their drug delivery systems have unique advantages for the treatment of bone tumors.…”

“…Bone-modifying agents with a high affinity for bone are used for active bone targeting, including alendronate, 144 – 146 zoledronic acid, 147 – 149 aspartic acid, 150 denosumab, 151 and aptamers. 152 , 153 Nanomaterials and their drug delivery systems have unique advantages for the treatment of bone tumors.…”

Recent Advances in Tannic Acid (Gallotannin) Anticancer Activities and Drug Delivery Systems for Efficacy Improvement; A Comprehensive Review

“…TA/polyvinylpyrilidone/zoledronic acid self-assembled nanoparticles particle size of ca. 400 nm, targeted mice bones and prostate tumor tissues in an exvivostudy as well as enhanced drug delivery to tumor cells [ 68 ].…”

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

“…And targeted NPs provided all treated mice protection from bone lesions while 33% of the mice with nontargeted NPs treatment had bone lesions (Gdowski et al, 2017). Similarly, polymeric NPs or micelles encapsulating anticancer drugs, functionalized with ZA or ALN for homing bone, were designed in many other studies and demonstrated much higher efficiency and accumulation in bone than free drugs (Rudnick-Glick et al, 2016;Hatami et al, 2019;Liu, Romanova, et al, 2019). A novel preparation of polymeric NPs with high affinity to bone was completed by Yuya Hirano et al (Hirano & Iwasaki, 2017).…”

“…In the affinity assay for HA in vitro , 77.5% of alendronate (ALN, Ald, or Alen) bound to HA powder (Ryu et al., 2016 ). Zol exhibited 20-fold increased targeting of bone metastatic lesions than other major tissues (Hatami et al., 2019 ). BP was used mostly to modify the designed NPs which encapsulated anticancer drugs.…”