Inhibition of Multidrug Resistance of Cancer Cells by Co‐Delivery of DNA Nanostructures and Drugs Using Porous Silicon Nanoparticles@Giant Liposomes

Biocompatible, multifunctional, stimuli responsive, and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes are assembled on a microfluidic chip as an advanced nano‐in‐micro platform (PSi NPs@giant liposomes), which can co‐load and co‐deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods, and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness show good biocompatibility, high loading capacity, and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. It is demonstrated that the DAO‐E A B⌢ DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin‐resistant MCF‐7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano‐in‐micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual responsiveness.

[1]  Qiao Jiang,et al.  DNA origami as an in vivo drug delivery vehicle for cancer therapy. , 2014, ACS nano.

[2]  Mauro Ferrari,et al.  Multi-stage delivery nano-particle systems for therapeutic applications. , 2011, Biochimica et biophysica acta.

[3]  R. Misra,et al.  Biomaterials , 2008 .

[4]  Mingtan Hai,et al.  Microfluidics fabrication of monodisperse biocompatible phospholipid vesicles for encapsulation and delivery of hydrophilic drug or active compound. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[5]  Jarno Salonen,et al.  Nanostructured Porous Silicon‐Solid Lipid Nanocomposite: Towards Enhanced Cytocompatibility and Stability, Reduced Cellular Association, and Prolonged Drug Release , 2013 .

[6]  B. Al-Lazikani,et al.  Combinatorial drug therapy for cancer in the post-genomic era , 2012, Nature Biotechnology.

[7]  K. Hagino-Yamagishi,et al.  [Oncogene]. , 2019, Gan to kagaku ryoho. Cancer & chemotherapy.

[8]  Mauro Ferrari,et al.  Sustained small interfering RNA delivery by mesoporous silicon particles. , 2010, Cancer research.

[9]  X. Wu,et al.  Nanotechnology applications for improved delivery of antiretroviral drugs to the brain. , 2010, Advanced drug delivery reviews.

[10]  H. Santos,et al.  Multifunctional porous silicon for therapeutic drug delivery and imaging. , 2011, Current drug discovery technologies.

[11]  Sebastian Seiffert,et al.  Microfluidic Synthesis of Advanced Microparticles for Encapsulation and Controlled Release{ a Introduction Lab on a Chip , 2022 .

[12]  V. Torchilin Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[13]  Vesa-Pekka Lehto,et al.  Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery. , 2014, Small.

[14]  W. Greco,et al.  The search for synergy: a critical review from a response surface perspective. , 1995, Pharmacological reviews.

[15]  Robert J. Lee,et al.  Vascular targeting of doxorubicin using cationic liposomes. , 2007, International journal of pharmaceutics.

[16]  T. Wei,et al.  Inhibition of Cancer Cell Migration by Gold Nanorods: Molecular Mechanisms and Implications for Cancer Therapy , 2014 .

[17]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[18]  Peisheng Xu,et al.  Multicompartment Intracellular Self‐Expanding Nanogel for Targeted Delivery of Drug Cocktail , 2012, Advanced materials.

[19]  D. Ruden,et al.  Possible effects of early treatments of hsp90 inhibitors on preventing the evolution of drug resistance to other anti-cancer drugs. , 2007, Current medicinal chemistry.

[20]  Mauro Ferrari,et al.  Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. , 2008, Nature nanotechnology.

[21]  M. Ferrari,et al.  Drug Delivery: Discoidal Porous Silicon Particles: Fabrication and Biodistribution in Breast Cancer Bearing Mice (Adv. Funct. Mater. 20/2012) , 2012 .

[22]  Daeyeon Lee,et al.  Double emulsion templated monodisperse phospholipid vesicles. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[23]  N. Seeman,et al.  Design and self-assembly of two-dimensional DNA crystals , 1998, Nature.

[24]  Sanyog Jain,et al.  Oral delivery of doxorubicin using novel polyelectrolyte-stabilized liposomes (layersomes). , 2012, Molecular pharmaceutics.

[25]  Huaimin Wang,et al.  Conjugation of two complementary anti-cancer drugs confers molecular hydrogels as a co-delivery system. , 2012, Chemical communications.

[26]  T. Chou Drug combination studies and their synergy quantification using the Chou-Talalay method. , 2010, Cancer research.

[27]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[28]  Beat Ernst,et al.  Drug discovery today. , 2003, Current topics in medicinal chemistry.

[29]  Xiaohua Huang,et al.  Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications , 2009, Advanced materials.

[30]  Jarno Salonen,et al.  Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy. , 2015, Biomaterials.

[31]  Elazer R. Edelman,et al.  Adv. Drug Delivery Rev. , 1997 .

[32]  R. Bellamkonda,et al.  Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods. , 2011, ACS nano.

[33]  S. Wereley,et al.  Soft Matter , 2014 .

[34]  Sun‐mi Lee,et al.  Synergistic Cancer Therapeutic Effects of Locally Delivered Drug and Heat Using Multifunctional Nanoparticles , 2010, Advanced materials.

[35]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[36]  Faqi Li,et al.  Engineering Inorganic Nanoemulsions/Nanoliposomes by Fluoride‐Silica Chemistry for Efficient Delivery/Co‐Delivery of Hydrophobic Agents , 2012 .

[37]  Bin Yang,et al.  Positively charged cholesterol derivative combined with liposomes as an efficient drug delivery system, in vitro and in vivo study , 2012 .

[38]  D. Russell,et al.  Label-free biosensing with lipid-functionalized gold nanorods. , 2011, Journal of the American Chemical Society.

[39]  W. Kaelin The Concept of Synthetic Lethality in the Context of Anticancer Therapy , 2005, Nature Reviews Cancer.

[40]  Jarno Salonen,et al.  Fabrication of a Multifunctional Nano‐in‐micro Drug Delivery Platform by Microfluidic Templated Encapsulation of Porous Silicon in Polymer Matrix , 2014, Advanced materials.

[41]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[42]  James Chen Yong Kah,et al.  Exploiting the protein corona around gold nanorods for loading and triggered release. , 2012, ACS nano.

[43]  H. Santos,et al.  Drug permeation across intestinal epithelial cells using porous silicon nanoparticles. , 2011, Biomaterials.

[44]  M. Shoichet,et al.  Doxorubicin‐Conjugated Immuno‐Nanoparticles for Intracellular Anticancer Drug Delivery , 2009 .

[45]  Hao Yan,et al.  DNA origami as a carrier for circumvention of drug resistance. , 2012, Journal of the American Chemical Society.

[46]  K. Kitagawa,et al.  17-AAG, an Hsp90 inhibitor, causes kinetochore defects: a novel mechanism by which 17-AAG inhibits cell proliferation , 2006, Oncogene.

[47]  N. Voelcker,et al.  Porous Silicon Nanodiscs for Targeted Drug Delivery , 2015 .

[48]  Mauro Ferrari,et al.  Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics. , 2011, Accounts of chemical research.

[49]  Chunhai Fan,et al.  Functional DNA nanostructures for theranostic applications. , 2014, Accounts of chemical research.

[50]  María J. Vicent,et al.  Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines. , 2009, Advanced drug delivery reviews.