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Surface Charge-Switching Polymeric Nanoparticles for Bacterial Cell Wall-Targeted Delivery of Antibiotics
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    Surface Charge-Switching Polymeric Nanoparticles for Bacterial Cell Wall-Targeted Delivery of Antibiotics
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    Harvard-MIT Division of Health Sciences & Technology, Cambridge, Massachusetts 02139, United States
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    § Synthetic Biology Group, Department of Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
    *Address correspondence to [email protected]; [email protected]
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    ACS Nano

    Cite this: ACS Nano 2012, 6, 5, 4279–4287
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    https://doi.org/10.1021/nn3008383
    Published April 3, 2012
    Copyright © 2012 American Chemical Society

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    Bacteria have shown a remarkable ability to overcome drug therapy if there is a failure to achieve sustained bactericidal concentration or if there is a reduction in activity in situ. The latter can be caused by localized acidity, a phenomenon that can occur as a result of the combined actions of bacterial metabolism and the host immune response. Nanoparticles (NP) have shown promise in treating bacterial infections, but a significant challenge has been to develop antibacterial NPs that may be suitable for systemic administration. Herein we develop drug-encapsulated, pH-responsive, surface charge-switching poly(d,l-lactic-co-glycolic acid)-b-poly(l-histidine)-b-poly(ethylene glycol) (PLGA-PLH-PEG) nanoparticles for treating bacterial infections. These NP drug carriers are designed to shield nontarget interactions at pH 7.4 but bind avidly to bacteria in acidity, delivering drugs and mitigating in part the loss of drug activity with declining pH. The mechanism involves pH-sensitive NP surface charge switching, which is achieved by selective protonation of the imidazole groups of PLH at low pH. NP binding studies demonstrate pH-sensitive NP binding to bacteria with a 3.5 ± 0.2- to 5.8 ± 0.1-fold increase in binding to bacteria at pH 6.0 compared to 7.4. Further, PLGA-PLH-PEG-encapsulated vancomycin demonstrates reduced loss of efficacy at low pH, with an increase in minimum inhibitory concentration of 1.3-fold as compared to 2.0-fold and 2.3-fold for free and PLGA-PEG-encapsulated vancomycin, respectively. The PLGA-PLH-PEG NPs described herein are a first step toward developing systemically administered drug carriers that can target and potentially treat Gram-positive, Gram-negative, or polymicrobial infections associated with acidity.

    Copyright © 2012 American Chemical Society

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    Detailed procedure for polymer synthesis, polymer characterization, and nanoparticle preparation; drug release kinetics; nanoparticle interactions with human cells including toxicity, binding as a function of pH, and binding kinetics; effect of PLH degree of polymerization on surface charge switching and bacterial binding. This material is available free of charge via the Internet at http://pubs.acs.org.

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    50. Mahmoud Elsabahy, Gyu Seong Heo, Soon-Mi Lim, Guorong Sun, and Karen L. Wooley . Polymeric Nanostructures for Imaging and Therapy. Chemical Reviews 2015, 115 (19) , 10967-11011. https://doi.org/10.1021/acs.chemrev.5b00135
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    53. Bradley Duncan, Xiaoning Li, Ryan F. Landis, Sung Tae Kim, Akash Gupta, Li-Sheng Wang, Rajesh Ramanathan, Rui Tang, Jeffrey A. Boerth, and Vincent M. Rotello . Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms. ACS Nano 2015, 9 (8) , 7775-7782. https://doi.org/10.1021/acsnano.5b01696
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    55. Daryl Sivakumaran, Eva Mueller, and Todd Hoare . Temperature-Induced Assembly of Monodisperse, Covalently Cross-Linked, and Degradable Poly(N-isopropylacrylamide) Microgels Based on Oligomeric Precursors. Langmuir 2015, 31 (21) , 5767-5778. https://doi.org/10.1021/acs.langmuir.5b01421
    56. Nora Francini, Laura Purdie, Cameron Alexander, Giuseppe Mantovani, and Sebastian G. Spain . Multifunctional Poly[N-(2-hydroxypropyl)methacrylamide] Copolymers via Postpolymerization Modification and Sequential Thiol–Ene Chemistry. Macromolecules 2015, 48 (9) , 2857-2863. https://doi.org/10.1021/acs.macromol.5b00447
    57. Benjamin Horev, Marlise I. Klein, Geelsu Hwang, Yong Li, Dongyeop Kim, Hyun Koo, and Danielle S. W. Benoit . pH-Activated Nanoparticles for Controlled Topical Delivery of Farnesol To Disrupt Oral Biofilm Virulence. ACS Nano 2015, 9 (3) , 2390-2404. https://doi.org/10.1021/nn507170s
    58. Li-Li Li, Jun-Hua Xu, Guo-Bin Qi, Xingzhong Zhao, Faquan Yu, and Hao Wang . Core–Shell Supramolecular Gelatin Nanoparticles for Adaptive and “On-Demand” Antibiotic Delivery. ACS Nano 2014, 8 (5) , 4975-4983. https://doi.org/10.1021/nn501040h
    59. B. V. V. S. Pavan Kumar, Krishnachary Salikolimi, and M. Eswaramoorthy . Glucose- and pH-Responsive Charge-Reversal Surfaces. Langmuir 2014, 30 (16) , 4540-4544. https://doi.org/10.1021/la500407r
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    67. Ximing Deng, Jinyao Zhou, Wei Fang, Rao Sun, Guoqing Yan, Yun Sun. pH-triggered small molecule nanodrugs self-assembled from tryptamine-cinnamaldehyde and fisetin for targeted sepsis-associated encephalopathy therapy. Journal of Biomaterials Applications 2025, 39 (10) , 1165-1176. https://doi.org/10.1177/08853282251318052
    68. Greta Kaspute, Arunas Zebrauskas, Akvile Streckyte, Tatjana Ivaskiene, Urte Prentice. Combining Advanced Therapies with Alternative Treatments: A New Approach to Managing Antimicrobial Resistance?. Pharmaceutics 2025, 17 (5) , 648. https://doi.org/10.3390/pharmaceutics17050648
    69. Xinyu Wang, Qingbin He, Lining Wang, Chengzhilin Li, Wenyu Zhang, Zhonghou Rong, Qingqing Yin, Yingchun Zhao. Acid responsive molybdenum (Mo)-based nanoparticles inhibit the cGAS-STING signaling pathway for sepsis therapy. Biomaterials Science 2025, 13 (9) , 2410-2421. https://doi.org/10.1039/D5BM00007F
    70. Chenlong Wang, S. M. Shatil Shahriar, Yajuan Su, Jingwei Xie. Versatile nanomaterials used in combatting biofilm infections. Nanomedicine 2025, 20 (5) , 501-518. https://doi.org/10.1080/17435889.2025.2459049
    71. Vidhi Bidaliya, Md Reyaz Alam, Anjalee Bhratee, Mayank Kumar, Piyush Anand, Pooja A. Chawla, Shamsher Singh. Advanced drug delivery systems in the management of CNS disorders. 2025, 429-449. https://doi.org/10.1016/B978-0-443-13474-6.00020-2
    72. Nancy Gurawalia, Preeti Thakur, Atul Thakur, Nikhil Bhalla. Nanoferrites as antibacterial and antifungal agents. 2025, 283-311. https://doi.org/10.1016/B978-0-443-22232-0.00013-7
    73. Shadab Dabagh, Roshan Javanifar, Murat Kaya, Aliakbar Ebrahimi, Sinan Güven, Burak Malik Kaya, Okan Esenturk, Aysegül Askin, Fatma Doğan Güzel, Onur Uysal, Ayla Eker Sarıboyacı, Hamed Ghorbanpoor, Huseyin Avci. Electrosprayed MnFe2O4/PVDF membrane integrated microfluidic chip for amoxicillin removal with real-time monitoring of pH and dissolved oxygen. Journal of Environmental Chemical Engineering 2024, 12 (6) , 114895. https://doi.org/10.1016/j.jece.2024.114895
    74. Yujing Huang, Xiaohan Guo, Yi Wu, Xingyu Chen, Lixiang Feng, Na Xie, Guobo Shen. Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment. Signal Transduction and Targeted Therapy 2024, 9 (1) https://doi.org/10.1038/s41392-024-01745-z
    75. Chuying Feng, Chen Sun, Emmanuel A Ho. Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis. Nanotechnology 2024, 35 (47) , 475101. https://doi.org/10.1088/1361-6528/ad7143
    76. Bo Zhang, Derong Lu, Dennis Bao Rong Wang, Zhi Yuan Kok, Mary B. Chan‐Park, Hongwei Duan. Enzyme‐Responsive Polyion Complex Nanoparticles of Cationic Antimicrobials for Activatable Antibacterial Therapy. Advanced Functional Materials 2024, 34 (46) https://doi.org/10.1002/adfm.202407869
    77. Rui Ding, Zhang Yuan, Ke Wang, Pandi Peng, Jiaheng Liang, Kun Wang, Ke Lin, Hanxue Wu, Peng Li. Dual-functional polyetheretherketone surface modification for enhanced osseointegration and antibacterial activity in pH-responsive manner. Journal of Materials Science & Technology 2024, 200 , 129-140. https://doi.org/10.1016/j.jmst.2024.02.054
    78. Charles Oluwaseun Adetunji, Olalekan Akinbo, John Tsado Mathew, Chukwuebuka Egbuna, Abel Inobeme, Olotu Titilayo, Olulope Olufemi Ajayi, Wadazani Dauda, Shakira Ghazanfar, Frank Abimbola Ogundolie, Julinan Bunmi Adetunji, Babatunde Oluwafemi Adetuyi, Shakirat Oloruntoyin Ajenifujah‐Solebo, Abdullahi Tunde Aborode. Nanotechnology. 2024, 1-17. https://doi.org/10.1002/9781394234769.ch15
    79. XiaoJie HU, LingYu ZHANG, YouYing SHENG, YanZheng GAO. Two-edged effects of micro/nanomaterials on the formation and spread of bacterial antibiotic resistance. SCIENTIA SINICA Technologica 2024, 54 (10) , 1888-1903. https://doi.org/10.1360/SST-2024-0067
    80. Habib Khan, Zahoor Jan, Inam Ullah, Abdullah Alwabli, Faisal Alharbi, Shabana Habib, Muhammad Islam, Byung-Joo Shin, Mi Young Lee, JaKeoung Koo. A deep dive into AI integration and advanced nanobiosensor technologies for enhanced bacterial infection monitoring. Nanotechnology Reviews 2024, 13 (1) https://doi.org/10.1515/ntrev-2024-0056
    81. Xiaojie Chen, Di Wu, Zhong Chen. Biomedical applications of stimuli‐responsive nanomaterials. MedComm 2024, 5 (8) https://doi.org/10.1002/mco2.643
    82. Wei Wang, Wanying Mo, Xue Xiao, Manying Cai, Songfu Feng, Yupeng Wang, Dongfang Zhou. Antibiotic-loaded lactoferrin nanoparticles as a platform for enhanced infection therapy through targeted elimination of intracellular bacteria. Asian Journal of Pharmaceutical Sciences 2024, 19 (4) , 100926. https://doi.org/10.1016/j.ajps.2024.100926
    83. Sudhanshu Mishra, Saumyatika Gantayat, Chandrajeet Dhara, Ayush Bhatt, Monika Singh, Sekar Vijayakumar, Minakshi Rajput. Advances in bioinspired nanomaterials managing microbial biofilms and virulence: A critical analysis. Microbial Pathogenesis 2024, 193 , 106738. https://doi.org/10.1016/j.micpath.2024.106738
    84. Haofei Li, Longlong Yang, Wenli Feng, Weilin Liu, Meng Wang, Fang Liu, Guofeng Li, Xing Wang. Poly(amino acid)-based drug delivery nanoparticles eliminate Methicillin resistant Staphylococcus aureus via tunable release of antibiotic. Colloids and Surfaces B: Biointerfaces 2024, 239 , 113882. https://doi.org/10.1016/j.colsurfb.2024.113882
    85. Cristiane Kalinke, Paulo R. de Oliveira, Luiz H. Marcolino-Júnior, Márcio F. Bergamini. Nanostructures of Prussian blue supported on activated biochar for the development of a glucose biosensor. Talanta 2024, 274 , 126042. https://doi.org/10.1016/j.talanta.2024.126042
    86. Yinan Jia, Li Zhang, Junhua Xu, Lin Xiang. Recent advances in cell membrane camouflaged nanotherapeutics for the treatment of bacterial infection. Biomedical Materials 2024, 19 (4) , 042006. https://doi.org/10.1088/1748-605X/ad46d4
    87. Linda Maurizi, Alba Lasalvia, Maria Gioia Fabiano, Eleonora D’Intino, Francesca Del Cioppo, Caterina Fraschetti, Antonello Filippi, Maria Grazia Ammendolia, Antonietta Lucia Conte, Jacopo Forte, Davide Corinti, Maria Elisa Crestoni, Maria Carafa, Carlotta Marianecci, Federica Rinaldi, Catia Longhi. Lentisk (Pistacia lentiscus) Oil Nanoemulsions Loaded with Levofloxacin: Phytochemical Profiles and Antibiofilm Activity against Staphylococcus spp.. Pharmaceutics 2024, 16 (7) , 927. https://doi.org/10.3390/pharmaceutics16070927
    88. Yue Yan, Shujie Li, Sa Chen, Zhou Zhou, Lian Li, Yuan Huang. Inflamed lung-targeting nanoparticles hijack activated platelets to alleviate lung injury in sepsis. Nano Research 2024, 18 (6) , 94907502. https://doi.org/10.26599/NR.2025.94907502
    89. Mohamed M. Hammouda, Abdulaziz A. Alanazi, Khaled M. Elattar. Mentha suaveolens Leaves Extract‐Mediated Synthesis of CoO@TiO 2 and Fe 2 O 3 @TiO 2 Core/Shell Nanoparticles with Synergistic Antimicrobial and Antioxidant Activities. ChemistrySelect 2024, 9 (17) https://doi.org/10.1002/slct.202401385
    90. Vijay Kumar Panthi, Kathryn E. Fairfull-Smith, Nazrul Islam. Liposomal drug delivery strategies to eradicate bacterial biofilms: Challenges, recent advances, and future perspectives. International Journal of Pharmaceutics 2024, 655 , 124046. https://doi.org/10.1016/j.ijpharm.2024.124046
    91. Charles Oluwaseun Adetunji, Olalekan Akinbo, John Tsado Mathew, Chukwuebuka Egbuna, Abel Inobeme, Olotu Titilayo, Olulope Olufemi Ajayi, Wadazani Dauda, Shakira Ghazanfar, Frank Abimbola Ogundolie, Julinan Bunmi Adetunji, Babatunde Oluwafemi Adetuyi, Shakirat Oloruntoyin Ajenifujah‐Solebo, Abdullahi Tunde Aborode. Nanotechnology. 2024, 1-17. https://doi.org/10.1002/9781119836513.ch1
    92. Paul Joshua Hurst, Kyle J. Gassaway, Mohammed Faris Abouchaleh, Nehal S. Idris, Chelsea R. Jones, Chris A. Dicksion, James S. Nowick, Joseph P. Patterson. Drug catalyzed polymerization yields one pot nanomedicines. RSC Applied Polymers 2024, 2 (2) , 238-247. https://doi.org/10.1039/D3LP00135K
    93. Kush N. Shah, Parth N. Shah, Francesca O. Agobe, Kaitlyn Lovato, Hongyin Gao, Oluwadara Ogun, Cason Hoffman, Marium Yabe-Gill, Qingquan Chen, Jordan Sweatt, Bhagath Chirra, Ricardo Muñoz-Medina, Delaney E. Farmer, László Kürti, Carolyn L. Cannon, . Antimicrobial activity of a natural compound and analogs against multi-drug-resistant Gram-positive pathogens. Microbiology Spectrum 2024, 12 (3) https://doi.org/10.1128/spectrum.01515-22
    94. Eman A. Ismail, Calvin A. Omolo, Mohammed A. Gafar, Rene Khan, Vincent O. Nyandoro, Elliasu Y. Salifu, Thirumala Govender. Multi-functional pH-responsive and biomimetic chitosan-based nanoplexes for targeted delivery of ciprofloxacin against bacterial sepsis. International Journal of Biological Macromolecules 2024, 262 , 130046. https://doi.org/10.1016/j.ijbiomac.2024.130046
    95. Nawras Osman, Calvin A Omolo, Mohammed A Gafar, Nikita Devnarain, Sanjeev Rambharose, Usri H Ibrahim, Victoria O Fasiku, Thirumala Govender. Niosomes modified with a novel pH-responsive coating (mPEG-OA) enhance the antibacterial and anti-biofilm activity of vancomycin against methicillin-resistant Staphylococcus aureus. Nano Express 2024, 5 (1) , 015008. https://doi.org/10.1088/2632-959X/ad1d02
    96. Parth Kadakia, Jules D. P. Valentin, Linda Hong, Samuel Watts, Owais Abdul Hameed, Michael Walch, Stefan Salentinig. Biocompatible Rhamnolipid Self‐Assemblies with pH‐Responsive Antimicrobial Activity. Advanced Healthcare Materials 2024, 13 (4) https://doi.org/10.1002/adhm.202302596
    97. Giulia Kassab, Neha Manav, Layla Pires, Miffy H. Y. Cheng, Yulin Mo, Hilde H. Buzzá, Iti Gupta, Juan Chen, Gang Zheng. Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy. Small Science 2024, 4 (2) https://doi.org/10.1002/smsc.202300131
    98. Gulsah Bakirdogen, Emine Selcuk, Elif L. Sahkulubey Kahveci, Tulin Ozbek, Serap Derman, Muhammet U. Kahveci. Fabrication of poly(β-amino ester) and hyaluronic acid based pH responsive nanocomplex as an antibiotic release system. International Journal of Biological Macromolecules 2024, 258 , 129060. https://doi.org/10.1016/j.ijbiomac.2023.129060
    99. Yu Zhao, Mengge Yuan, Haowei Yang, Jie Li, Yulong Ying, Jinhua Li, Weihao Wang, Sheng Wang. Versatile Multi‐Wavelength Light‐Responsive Metal‐Organic Frameworks Micromotor through Porphyrin Metalation for Water Sterilization. Small 2024, 20 (2) https://doi.org/10.1002/smll.202305189
    100. N. Prabhu, S. Nivetha, G. Pooja, B. Nivedhitha, M. Baskamary, S. Pooja. Mycosynthesis of Nanoparticles and Their Application in Medicine. 2024, 207-226. https://doi.org/10.1007/978-3-031-45956-6_8
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    Cite this: ACS Nano 2012, 6, 5, 4279–4287
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    https://doi.org/10.1021/nn3008383
    Published April 3, 2012
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