Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

[1]  Liangzhu Feng,et al.  Intelligent Albumin–MnO2 Nanoparticles as pH‐/H2O2‐Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy , 2016, Advanced materials.

[2]  Liangzhu Feng,et al.  Light‐Responsive, Singlet‐Oxygen‐Triggered On‐Demand Drug Release from Photosensitizer‐Doped Mesoporous Silica Nanorods for Cancer Combination Therapy , 2016 .

[3]  Raghavendra Kikkeri,et al.  Glyco-gold nanoparticle shapes enhance carbohydrate-protein interactions in mammalian cells. , 2016, Nanoscale.

[4]  Xian‐Zheng Zhang,et al.  Acidity‐Triggered Tumor‐Targeted Chimeric Peptide for Enhanced Intra‐Nuclear Photodynamic Therapy , 2016 .

[5]  Jun Wang,et al.  Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy , 2016, Proceedings of the National Academy of Sciences.

[6]  C. Yun,et al.  Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation. , 2016, Angewandte Chemie.

[7]  David J. Lunn,et al.  Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in Aqueous Media. , 2016, Journal of the American Chemical Society.

[8]  Yanli Zhao,et al.  Charge-Convertible Carbon Dots for Imaging-Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency. , 2016, ACS nano.

[9]  G. Stassi,et al.  Epithelial–mesenchymal transition: a new target in anticancer drug discovery , 2016, Nature Reviews Drug Discovery.

[10]  Song Shen,et al.  Tumor Acidity-Sensitive Polymeric Vector for Active Targeted siRNA Delivery. , 2015, Journal of the American Chemical Society.

[11]  María Vallet-Regí,et al.  Polymer-Grafted Mesoporous Silica Nanoparticles as Ultrasound-Responsive Drug Carriers. , 2015, ACS nano.

[12]  Shibo Wang,et al.  Ratiometric Biosensor for Aggregation-Induced Emission-Guided Precise Photodynamic Therapy. , 2015, ACS nano.

[13]  R. Bhosale,et al.  A simple zinc-porphyrin-NDI dyad system generates a light energy to proton potential across a lipid membrane , 2015 .

[14]  Christopher V. Barback,et al.  Therapeutic Enzyme‐Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors , 2015, Advanced materials.

[15]  Kai Han,et al.  Activable Cell-Penetrating Peptide Conjugated Prodrug for Tumor Targeted Drug Delivery. , 2015, ACS applied materials & interfaces.

[16]  Xian‐Zheng Zhang,et al.  Dual-pH Sensitive Charge-Reversal Polypeptide Micelles for Tumor-Triggered Targeting Uptake and Nuclear Drug Delivery. , 2015, Small.

[17]  Xian‐Zheng Zhang,et al.  Dual‐Stage‐Light‐Guided Tumor Inhibition by Mitochondria‐Targeted Photodynamic Therapy , 2015 .

[18]  H. Kong,et al.  Non-Spherical Particles for Targeted Drug Delivery. , 2015, Chemical engineering science.

[19]  S. Bhosale,et al.  Solvent-Tuned Self-Assembled Nanostructures of Chiral l/d-Phenylalanine Derivatives of Protoporphyrin IX , 2015, ChemistryOpen.

[20]  Qi Lei,et al.  A Tumor Targeted Chimeric Peptide for Synergistic Endosomal Escape and Therapy by Dual‐Stage Light Manipulation , 2015 .

[21]  R. Zhuo,et al.  A FRET‐Based Dual‐Targeting Theranostic Chimeric Peptide for Tumor Therapy and Real‐time Apoptosis Imaging , 2014, Advanced healthcare materials.

[22]  Andrew L. Ferguson,et al.  Investigating the optimal size of anticancer nanomedicine , 2014, Proceedings of the National Academy of Sciences.

[23]  Liang Cheng,et al.  Functional nanomaterials for phototherapies of cancer. , 2014, Chemical reviews.

[24]  Eun Seong Lee,et al.  Surface charge switching nanoparticles for magnetic resonance imaging. , 2014, International journal of pharmaceutics.

[25]  Wei Huang,et al.  Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug-drug conjugate for cancer therapy. , 2014, Journal of the American Chemical Society.

[26]  E. Gawalt,et al.  Coassembly of amphiphilic peptide EAK16-II with histidinylated analogues and implications for functionalization of β-sheet fibrils in vivo. , 2014, Biomaterials.

[27]  Xin Cai,et al.  Radioactive 198Au-Doped Nanostructures with Different Shapes for In Vivo Analyses of Their Biodistribution, Tumor Uptake, and Intratumoral Distribution , 2014, ACS nano.

[28]  Jiwei Cui,et al.  Nanoscale engineering of low-fouling surfaces through polydopamine immobilisation of zwitterionic peptides. , 2014, Soft matter.

[29]  Patrick Couvreur,et al.  Stimuli-responsive nanocarriers for drug delivery. , 2013, Nature materials.

[30]  S. V. Sreenivasan,et al.  Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms , 2013, Proceedings of the National Academy of Sciences.

[31]  Zhishen Ge,et al.  Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. , 2013, Chemical Society reviews.

[32]  S. Bhosale,et al.  Supramolecular Chemistry of Protoporphyrin IX and Its Derivatives (Eur. J. Org. Chem. 19/2013) , 2013 .

[33]  Hua Wei,et al.  Design and development of polymeric micelles with cleavable links for intracellular drug delivery , 2013 .

[34]  A. Jones,et al.  Nanoparticle geometry and surface orientation influence mode of cellular uptake. , 2013, ACS nano.

[35]  Samir Mitragotri,et al.  Particle shape enhances specificity of antibody-displaying nanoparticles , 2013, Proceedings of the National Academy of Sciences.

[36]  S. Bhosale,et al.  Solvent induced ordered-supramolecular assembly of highly branched protoporphyrin IX derivative , 2012 .

[37]  José M. Morachis,et al.  Physical and Chemical Strategies for Therapeutic Delivery by Using Polymeric Nanoparticles , 2012, Pharmacological Reviews.

[38]  Bing Xu,et al.  Imaging enzyme-triggered self-assembly of small molecules inside live cells , 2012, Nature Communications.

[39]  S. Bhosale,et al.  Supramolecular self-assembled nanowires by the aggregation of a protoporphyrin derivative in low-polarity solvents , 2011 .

[40]  Zongxi Li,et al.  Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism. , 2011, ACS nano.

[41]  S. Bhosale,et al.  RETRACTED ARTICLE Supramolecular self-assembly of protoporphyrin IX amphiphiles into worm-like and particular aggregates , 2011 .

[42]  Shaoyi Jiang,et al.  Ultra-low fouling peptide surfaces derived from natural amino acids. , 2009, Biomaterials.

[43]  Andrew M. Smith,et al.  Designing peptide based nanomaterials. , 2008, Chemical Society reviews.

[44]  J. Duhamel,et al.  Protection of oligodeoxynucleotides against nuclease degradation through association with self-assembling peptides. , 2008, Biomaterials.

[45]  A. Herrmann,et al.  Cellular Uptake of DNA Block Copolymer Micelles with Different Shapes , 2008 .

[46]  O. Farokhzad,et al.  Nanocarriers as an emerging platform for cancer therapy. , 2007, Nature nanotechnology.

[47]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[48]  R. Cardone,et al.  The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis , 2005, Nature Reviews Cancer.

[49]  Peter B Jahrling,et al.  Exotic emerging viral diseases: progress and challenges , 2004, Nature Medicine.

[50]  I. Tannock,et al.  Acid pH in tumors and its potential for therapeutic exploitation. , 1989, Cancer research.

[51]  Shaobing Zhou,et al.  A Bio‐Inspired Rod‐Shaped Nanoplatform for Strongly Infecting Tumor Cells and Enhancing the Delivery Efficiency of Anticancer Drugs , 2016 .

[52]  Z. Qiao,et al.  One-pot synthesis of pH-sensitive poly(RGD-co-β-amino ester)s for targeted intracellular drug delivery , 2014 .

[53]  Dong Chen,et al.  The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. , 2010, Biomaterials.