Construction of Core-Cross-Linked Polymer Micelles with High Biocompatibility and Stability for pH/Reduction Controllable Drug Delivery.

Polymer micelles have been studied extensively in drug delivery systems (DDS), and their stability is well known to directly affect drug delivery. In this article, a series of amphiphilic copolymers LA-PDPAn-PVPm were synthesized to prepare core-cross-linked nanoparticles (CNP) applied to controllable and targeted anticancer drug delivery. The copolymers could self-assemble in aqueous solution and form homogeneous spherical micelles with particle sizes of between 100 and 150 nm. A comparison between un-cross-linked UCNP and CNP showed that the cross-linking of LA could significantly improve the stability and responsive ability of the nanoparticles. From the in vitro-simulated drug release experiments, CNP was found to have great drug blocking ability under normal physiological conditions and could achieve rapid and efficient drug release under acidic/reducing conditions. In addition, cell experiments showed that CNP had superior biocompatibility and could target tumor cells for drug release. In conclusion, a drug carrier based on copolymer LA-PDPA-PVP realized effective controlled drug release due to the cross-linking of LA. The results will provide guidance for the design strategy of polymer micelles for drug carriers.

[1]  Honglai Liu,et al.  Integration of Chemotherapy and Phototherapy Based on a pH/ROS/NIR Multi-Responsive Polymer-Modified MSN Drug Delivery System for Improved Antitumor Efficacy , 2023, SSRN Electronic Journal.

[2]  G. Yilmaz,et al.  Hierarchy of Complex Glycomacromolecules: From Controlled Topologies to Biomedical Applications. , 2022, Biomacromolecules.

[3]  S. Flora,et al.  Stimuli-responsive Polymeric nanosystems for therapeutic applications. , 2021, Current pharmaceutical design.

[4]  S. Ju,et al.  Stimuli-Responsive Polymeric Nanoplatforms for Cancer Therapy , 2021, Frontiers in Bioengineering and Biotechnology.

[5]  N. Kamaly,et al.  Meta-analysis of In Vitro Drug-Release Parameters Reveals Predictable and Robust Kinetics for Redox-Responsive Drug-Conjugated Therapeutic Nanogels , 2021 .

[6]  Shuling Yu,et al.  NIR-/pH-Responsive Nanocarriers Based on Mesoporous Hollow Polydopamine for Codelivery of Hydrophilic/Hydrophobic Drugs and Photothermal Synergetic Therapy. , 2021, ACS applied bio materials.

[7]  Mallesh Kurakula,et al.  Type of Article: REVIEW Pharmaceutical Assessment of Polyvinylpyrrolidone (PVP): As Excipient from Conventional to Controlled Delivery Systems with a Spotlight on COVID-19 Inhibition , 2020, Journal of Drug Delivery Science and Technology.

[8]  H. Roghani‐Mamaqani,et al.  Temperature-induced self-assembly of amphiphilic triblock terpolymers to low cytotoxic spherical and cubic structures as curcumin carriers , 2020, Journal of Molecular Liquids.

[9]  H. van Loveren,et al.  Re‐evaluation of polyvinylpyrrolidone (E 1201) and polyvinylpolypyrrolidone (E 1202) as food additives and extension of use of polyvinylpyrrolidone (E 1201) , 2020, EFSA journal. European Food Safety Authority.

[10]  A. Heidari,et al.  Poly(vinylidene fluoride) (PVDF) / PVDF‐ g ‐polyvinylpyrrolidone (PVP) / TiO 2 mixed matrix nanofiltration membranes: preparation and characterization , 2020 .

[11]  Honglai Liu,et al.  Double security drug delivery system DDS constructed by multi-responsive (pH/redox/US) microgel. , 2020, Colloids and surfaces. B, Biointerfaces.

[12]  T. Simić,et al.  Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy , 2020, Pharmaceutics.

[13]  Santosh Yadav,et al.  Nanoscale Self-Assembly for Therapeutic Delivery , 2020, Frontiers in Bioengineering and Biotechnology.

[14]  Mosa Alsehli,et al.  Polymeric nanocarriers as stimuli-responsive systems for targeted tumor (cancer) therapy: Recent advances in drug delivery , 2020, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[15]  V. Kozlovskaya,et al.  Self-Assemblies of Thermoresponsive Poly(N-vinylcaprolactam) Polymers for Applications in Biomedical Field , 2020 .

[16]  Yanqing Wang,et al.  Redox response, antibacterial and drug package capacities of chitosan-α-lipoic acid conjugates. , 2019, International journal of biological macromolecules.

[17]  Da Huo,et al.  Recent Advances in Nanostrategies Capable of Overcoming Biological Barriers for Tumor Management , 2019, Advanced materials.

[18]  D. Xie,et al.  Surface modification of polyurethane with a hydrophilic, antibacterial polymer for improved antifouling and antibacterial function , 2018, Journal of biomaterials applications.

[19]  Yaping Li,et al.  Rational Design of Nanoparticles with Deep Tumor Penetration for Effective Treatment of Tumor Metastasis , 2018, Advanced Functional Materials.

[20]  K. Landfester,et al.  The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery , 2018, Front. Immunol..

[21]  K. Landfester,et al.  Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona , 2018, Nature Nanotechnology.

[22]  Eric A. Appel,et al.  Single-Chain Polymeric Nanocarriers: A Platform for Determining Structure-Function Correlations in the Delivery of Molecular Cargo. , 2017, Biomacromolecules.

[23]  Chunsheng Xiao,et al.  Multi-responsive core-crosslinked poly (thiolether ester) micelles for smart drug delivery , 2017 .

[24]  Jian Zhang,et al.  Robust, active tumor-targeting and fast bioresponsive anticancer nanotherapeutics based on natural endogenous materials. , 2016, Acta biomaterialia.

[25]  P. Liu,et al.  Leakage-free DOX/PEGylated chitosan micelles fabricated via facile one-step assembly for tumor intracellular pH-triggered release. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[26]  R. Kalluri.  The biology and function of fibroblasts in cancer , 2016, Nature Reviews Cancer.

[27]  M. Sawamoto,et al.  Precision Self-Assembly of Amphiphilic Random Copolymers into Uniform and Self-Sorting Nanocompartments in Water , 2016 .

[28]  Honglai Liu,et al.  Incorporation of Amphipathic Diblock Copolymer in Lipid Bilayer for Improving pH Responsiveness , 2016 .

[29]  D. Munn,et al.  Immune suppressive mechanisms in the tumor microenvironment. , 2016, Current opinion in immunology.

[30]  Iole Venditti,et al.  Role of nanostructured polymers on the improvement of electrical response-based relative humidity sensors , 2016 .

[31]  Mauro Ferrari,et al.  Principles of nanoparticle design for overcoming biological barriers to drug delivery , 2015, Nature Biotechnology.

[32]  Zhiyuan Zhong,et al.  Reversibly crosslinked hyaluronic acid nanoparticles for active targeting and intelligent delivery of doxorubicin to drug resistant CD44+ human breast tumor xenografts. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[33]  Guoying Zhang,et al.  Spatiotemporal monitoring endocytic and cytosolic pH gradients with endosomal escaping pH-responsive micellar nanocarriers. , 2014, Biomacromolecules.

[34]  Jintian Tang,et al.  Pharmaceutical nanotechnology for oral delivery of anticancer drugs. , 2013, Advanced drug delivery reviews.

[35]  Jianzhong Du,et al.  pH-Sensitive Block Copolymer Vesicles with Variable Trigger Points for Drug Delivery , 2012 .

[36]  K. Lim,et al.  Self‐Assembled Nanoparticles with Dual Effects of Passive Tumor Targeting and Cancer‐Selective Anticancer Effects , 2012 .

[37]  J. Pedraz,et al.  Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research , 2012, Clinical and Translational Oncology.

[38]  B. Sproat,et al.  PEGylation of biodegradable dextran nanogels for siRNA delivery. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[39]  Zhiyuan Zhong,et al.  pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: a comparative study with micelles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[40]  Yan Xu,et al.  Reduction-sensitive reversibly crosslinked biodegradable micelles for triggered release of doxorubicin. , 2009, Macromolecular bioscience.

[41]  John G. Lyons,et al.  Characterisation and controlled drug release from novel drug-loaded hydrogels. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[42]  R. Langer,et al.  Exploring polyethylenimine‐mediated DNA transfection and the proton sponge hypothesis , 2005, The journal of gene medicine.

[43]  Sébastien Lecommandoux,et al.  Reversible inside-out micellization of pH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. , 2005, Journal of the American Chemical Society.

[44]  B. Collins,et al.  Polyvinyl Pyrrolidone: A Novel Cryoprotectant in Islet Cell Cryopreservation1 , 2004, Cell transplantation.

[45]  Zhiqiang Yu,et al.  Stimuli-responsive nanotherapeutics for precision drug delivery and cancer therapy. , 2019, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.