Bone metastasis target redox-responsive micell for the treatment of lung cancer bone metastasis and anti-bone resorption

Abstract In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and −15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis. Graphical Abstract

[1]  B. Prabhakarpandian,et al.  A Biomimetic Microfluidic Tumor Microenvironment Platform Mimicking the EPR Effect for Rapid Screening of Drug Delivery Systems , 2017, Scientific Reports.

[2]  W. Mackenzie,et al.  Development of Bone Targeting Drugs , 2017, International journal of molecular sciences.

[3]  Q. Mei,et al.  Redox and pH dual sensitive bone targeting nanoparticles to treat breast cancer bone metastases and inhibit bone resorption. , 2017, Nanoscale.

[4]  Q. Mei,et al.  Charge reversible calcium phosphate lipid hybrid nanoparticle for siRNA delivery , 2017, Oncotarget.

[5]  H. Santos,et al.  In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells. , 2017, Biomaterials.

[6]  Yanjuan Huang,et al.  Calcium phosphate nanoparticles functionalized with alendronate-conjugated polyethylene glycol (PEG) for the treatment of bone metastasis. , 2017, International journal of pharmaceutics.

[7]  Guangdong Zhou,et al.  Self-Assembly Assisted Fabrication of Dextran-Based Nanohydrogels with Reduction-Cleavable Junctions for Applications as Efficient Drug Delivery Systems , 2017, Scientific Reports.

[8]  V. Tzankova,et al.  Antioxidant response and biocompatibility of curcumin-loaded triblock copolymeric micelles , 2017, Toxicology mechanisms and methods.

[9]  S. M. Taghdisi,et al.  Dextran-poly lactide-co-glycolide polymersomes decorated with folate-antennae for targeted delivery of docetaxel to breast adenocarcinima in vitro and in vivo. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[10]  T. Heinze,et al.  Novel dextran derivatives with unconventional structure formed in an efficient one-pot reaction. , 2016, Carbohydrate research.

[11]  Sung‐Wook Choi,et al.  Bone-targeted delivery of nanodiamond-based drug carriers conjugated with alendronate for potential osteoporosis treatment. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[12]  Qian Li,et al.  Paclitaxel-Loaded Mixed Micelles Enhance Ovarian Cancer Therapy through Extracellular pH-Triggered PEG Detachment and Endosomal Escape. , 2016, Molecular pharmaceutics.

[13]  G. Makris,et al.  Development and Pharmacological Evaluation of New Bone-Targeted (99m)Tc-Radiolabeled Bisphosphonates. , 2016, Molecular pharmaceutics.

[14]  S. P. Walton,et al.  Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing. , 2016, Technology.

[15]  Mohammad Ramezani,et al.  Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Wenxiu He,et al.  Disulfide-Linked Amphiphilic Polymer-Docetaxel Conjugates Assembled Redox-Sensitive Micelles for Efficient Antitumor Drug Delivery. , 2016, Biomacromolecules.

[17]  Liping Zhang,et al.  Zwitterionic pH/redox nanoparticles based on dextran as drug carriers for enhancing tumor intercellular uptake of doxorubicin. , 2016, Materials science & engineering. C, Materials for biological applications.

[18]  Ang Li,et al.  Synthesis and Characterization of Cleavable Core-Cross-Linked Micelles Based on Amphiphilic Block Copolypeptoids as Smart Drug Carriers. , 2016, Biomacromolecules.

[19]  Q. Mei,et al.  Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer , 2015, Scientific Reports.

[20]  Ying‐Wei Yang,et al.  Layer-by-Layer (LBL) Self-Assembled Biohybrid Nanomaterials for Efficient Antibacterial Applications. , 2015, ACS applied materials & interfaces.

[21]  Hong Yuan,et al.  Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Qing Jiang,et al.  Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin , 2015, Journal of biomaterials science. Polymer edition.

[23]  D. Schuppan,et al.  Dextran-based therapeutic nanoparticles for hepatic drug delivery. , 2015, Nanomedicine.

[24]  C. Solans,et al.  Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies. , 2015, Nanoscale.

[25]  Yi Wang,et al.  Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles. , 2014, Biomaterials.

[26]  Xiaolan Zhang,et al.  PEG-Farnesyl Thiosalicylic Acid Telodendrimer Micelles as an Improved Formulation for Targeted Delivery of Paclitaxel , 2014, Molecular pharmaceutics.

[27]  K. Imai Alendronate sodium hydrate (oral jelly) for the treatment of osteoporosis: review of a novel, easy to swallow formulation , 2013, Clinical interventions in aging.

[28]  F. Kratz,et al.  Development of novel bisphosphonate prodrugs of doxorubicin for targeting bone metastases that are cleaved pH dependently or by cathepsin B: synthesis, cleavage properties, and binding properties to hydroxyapatite as well as bone matrix. , 2012, Journal of medicinal chemistry.

[29]  D. Chappard,et al.  Bone metastasis: histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review. , 2011, Morphologie : bulletin de l'Association des anatomistes.

[30]  Charity L. Washam,et al.  Bone metastasis: mechanisms and therapeutic opportunities , 2011, Nature Reviews Endocrinology.

[31]  Badriprasad Ananthanarayanan,et al.  Thermodynamic and kinetic stability of DSPE-PEG(2000) micelles in the presence of bovine serum albumin. , 2010, The journal of physical chemistry. B.

[32]  J. Tímár [Molecular basis of bone metastasis formation and its targeted therapy]. , 2010, Magyar onkologia.

[33]  S. Aluri,et al.  Environmentally responsive peptides as anticancer drug carriers. , 2009, Advanced drug delivery reviews.

[34]  J. Shea,et al.  Skeletal function and structure: implications for tissue-targeted therapeutics. , 2005, Advanced drug delivery reviews.

[35]  F. Ahsan,et al.  Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome. , 2015, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[36]  P. Płonka,et al.  Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study. , 2013, Acta biochimica Polonica.

[37]  L. Boothby Bisphosphonates for the Prevention and Treatment of Osteoporosis , 2003 .