Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles
Abstract
To elucidate the effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles (NPs), rhodamine B (RhB) labeled carboxymethyl chitosan grafted NPs (RhB-CMCNP) and chitosan hydrochloride grafted NPs (RhB-CHNP) were developed as the model negatively and positively charged polymeric NPs, respectively. These NPs owned well defined particle sizes (150-500 nm) and Zeta potentials (-40 mV - +35 mV). FITC labeled protamine sulfate (FITC-PS) loaded RhB-CMCNP and camptothecin (CPT) loaded RhB-CHNP with high encapsulation efficiency were prepared. The fluorescence stability in plasma and towards I(-) was investigated, and the result indicated it was sufficient for qualitative and quantitative analysis. NPs with high surface charge and large particle size were phagocytized more efficiently by murine macrophage. Slight particle size and surface charge differences and different cell lines had significant implications in the cellular uptake of NPs, and various mechanisms were involved in the uptake process. In vivo biodistribution suggested that NPs with slight negative charges and particle size of 150 nm were tended to accumulate in tumor more efficiently. These results could serve as a guideline in the rational design of drug nanocarriers with maximized therapeutic efficacy and predictable in vivo properties, in which the control of particle size and surface charge was of significance.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Uptake is higher in nanoparticles with high negative or positive surface charges.
“uptake is higher in nanoparticles with high negative or positive surface charges128.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [128]
Cites
Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells
Chithrani, D. B., Ghazani, A. A., & Chan, W. C. W. (2006) · Nano Letters · doi:10.1021/nl052396o · Cited by 4,887 · see citing works
Nanoparticle therapeutics: an emerging treatment modality for cancer
Davis, M. E., Chen, Z., & Shin, D. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2614 · Cited by 4,233 · see citing works
Regulated portals of entry into the cell
Conner, S. D., & Schmid, S. L. (2003) · Nature · doi:10.1038/nature01451 · Cited by 3,816 · see citing works
Factors affecting the clearance and biodistribution of polymeric nanoparticles
Alexis, F., Pridgen, E., Molnar, L. K., & Farokhzad, O. C. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800051m · Cited by 3,699 · see citing works
The effect of particle design on cellular internalization pathways
Gratton, S. E. A., Ropp, P. A., Pohlhaus, P. D., Luft, J. C., Madden, V. J., Napier, M. E., & DeSimone, J. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801763105 · Cited by 2,918 · see citing works
Rejman, J., Oberle, V., Zuhorn, I. S., & Hoekstra, D. (2004) · Biochemical Journal · doi:10.1042/bj20031253 · Cited by 2,872 · see citing works
Yin Win, K., & Feng, S.-S. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2004.07.050 · Cited by 1,452 · see citing works
Chitosan and Its Use as a Pharmaceutical Excipient
Ilium, L. (1998) · Pharmaceutical Research · doi:10.1023/a:1011929016601 · Cited by 1,400 · see citing works
Mechanics of receptor-mediated endocytosis
Gao, H., Shi, W., & Freund, L. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503879102 · Cited by 1,219 · see citing works
Size Effect on Cell Uptake in Well‐Suspended, Uniform Mesoporous Silica Nanoparticles
Lu, F., Wu, S., Hung, Y., & Mou, C. (2009) · Small · doi:10.1002/smll.200900005 · Cited by 1,040 · see citing works
Nanoparticles in cellular drug delivery
Faraji, A. H., & Wipf, P. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.02.043 · Cited by 907 · see citing works
Foged, C., Brodin, B., Frøkjær, S., & Sundblad, A. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2005.03.035 · Cited by 874 · see citing works
Harnessing actin dynamics for clathrin-mediated endocytosis
Kaksonen, M., Toret, C. P., & Drubin, D. G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1940 · Cited by 706 · see citing works
Osaki, F., Kanamori, T., Sando, S., Sera, T., & Aoyama, Y. (2004) · Journal of the American Chemical Society · doi:10.1021/ja048792a · Cited by 536 · see citing works
Polylysine-based transfection systems utilizing receptor-mediated delivery
Zauner, W., Ogris, M., & Wagner, E. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(97)00110-5 · Cited by 507 · see citing works
Liu, D., Mori, A., & Huang, L. (1992) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(92)90136-a · Cited by 464 · see citing works
In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density
Zauner, W., Farrow, N. A., & Haines, A. M. R. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(00)00358-8 · Cited by 411 · see citing works
Clift, M. J. D., Rothen‐Rutishauser, B., Brown, D. M., Duffin, R., Donaldson, K., Proudfoot, L., Guy, K., & Stone, V. (2008) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2008.06.009 · Cited by 358 · see citing works
Roser, M., Fischer, D., & Kissel, T. (1998) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(98)00038-1 · Cited by 357 · see citing works
Tan, M. L., Choong, P. F. M., & Dass, C. R. (2010) · Peptides · doi:10.1016/j.peptides.2009.10.002 · Cited by 350 · see citing works
Effect of nanoparticles on sessile droplet contact angle
Vafaei, S., Borca‐Tasciuc, T., Podowski, M. Z., et al. (2006) · Nanotechnology · doi:10.1088/0957-4484/17/10/014 · Cited by 211 · see citing works
Akiyama, Y., Mori, T., Katayama, Y., & Niidome, T. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.06.006 · Cited by 210 · see citing works
Lee, K.-D., Nir, S., & Papahadjopoulos, D. (1993) · Biochemistry · doi:10.1021/bi00054a021 · Cited by 204 · see citing works
Influence of polysaccharide coating on the interactions of nanoparticles with biological systems
Lemarchand, C., Gref, R., Passirani, C., Garcion, E., Petri, B., Müller, R. H., Costantini, D., & Couvreur, P. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.04.041 · Cited by 197 · see citing works
Chono, S., Tanino, T., Seki, T., & Morimoto, K. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.59.1.0010 · Cited by 190 · see citing works
Mao, S., Germershaus, O., Fischer, D., Linn, T., Schnepf, R., & Kissel, T. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-8175-y · Cited by 164 · see citing works
Cortez, C., Tomaskovic‐Crook, E., Johnston, A. P. R., et al. (2007) · ACS Nano · doi:10.1021/nn700060m · Cited by 158 · see citing works
3H Dendrimer Nanoparticle Organ/Tumor Distribution
Nigavekar, S. S., Sung, L. Y., Llanes, M., et al. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000019302.26097.cc · Cited by 149 · see citing works
Effect of nanoparticle size on sessile droplet contact angle
Munshi, A. M., Singh, V. N., Kumar, M., et al. (2008) · Journal of Applied Physics · doi:10.1063/1.2912464 · Cited by 138 · see citing works
Reddy, L. H., Sharma, R. K., Chuttani, K., et al. (2004) · The AAPS Journal · doi:10.1208/aapsj060323 · Cited by 132 · see citing works
Preparation and characterization of mucoadhesive polymer-coated nanoparticles
Cui, F., Qian, F., & Yin, C. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.02.031 · Cited by 122 · see citing works
Self-citationCharacteristics and biodistribution of cationic liposomes and their DNA complexes
Ishiwata, H., Suzuki, N., Ando, S., Kikuchi, H., & Kitagawa, T. (2000) · Journal of Controlled Release · doi:10.1016/s0168-3659(00)00293-5 · Cited by 117 · see citing works
Analysis of fluorescence quenching of new indole derivative by aniline using Stern–Volmer plots
Kumar, H. M. S., Kunabenchi, R. S., Biradar, J. S., et al. (2005) · Journal of Luminescence · doi:10.1016/j.jlumin.2005.02.012 · Cited by 99 · see citing works
Investigating Tryptophan Quenching of Fluorescein Fluorescence under Protolytic Equilibrium
Togashi, D. M., Szczupak, B., Ryder, A. G., Calvet, A., & O’Loughlin, M. (2009) · The Journal of Physical Chemistry A · doi:10.1021/jp808121y · Cited by 48 · see citing works
Weaver, D. J., & Voss, E. W. (1998) · Biology of the Cell · doi:10.1016/s0248-4900(98)80338-9 · Cited by 28 · see citing works
Borowik, T., Widerak, K., Ugorski, M., & Langner, M. (2005) · Journal of Liposome Research · doi:10.1080/08982100500364370 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Maeda, H., Nakamura, H., & Fang, J. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.10.002 · Cited by 2,376 · see citing works
The Effect of Nanoparticle Size on <i>In Vivo</i> Pharmacokinetics and Cellular Interaction
Hoshyar, N., Gray, S., Han, H., & Bao, G. (2016) · Nanomedicine · doi:10.2217/nnm.16.5 · Cited by 1,990 · see citing works
Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy
Pham, T. C., Nguyen, V.-N., Choi, Y., Lee, S., & Yoon, J. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00381 · Cited by 1,813 · see citing works
Rodell, C. B., Arlauckas, S. P., Cuccarese, M. F., Garris, C. S., Li, R., Ahmed, M. S., Kohler, R. H., Pittet, M. J., & Weissleder, R. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0236-8 · Cited by 1,099 · see citing works
Xiao, K., Li, Y., Luo, J., Lee, J. S., Xiao, W., Gonik, A. M., Agarwal, R. G., & Lam, K. S. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.021 · Cited by 1,039 · see citing works
Duan, X., & Li, Y. (2013) · Small · doi:10.1002/smll.201201390 · Cited by 926 · see citing works
A holistic approach to targeting disease with polymeric nanoparticles
Cheng, C. J., Tietjen, G. T., Saucier-Sawyer, J. K., & Saltzman, W. M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4503 · Cited by 480 · see citing works
Tumour‐associated macrophages act as a slow‐release reservoir of nano‐therapeutic Pt(IV) pro‐drug
Miller, M. A., Zheng, Y.-R., Gadde, S., Pfirschke, C., Zope, H., Engblom, C., Kohler, R. H., Iwamoto, Y., Yang, K. S., Askevold, B., et al. (2015) · Nature Communications · doi:10.1038/ncomms9692 · Cited by 441 · see citing works
Barriers to drug delivery in solid tumors
Sriraman, S. K., Aryasomayajula, B., & Torchilin, V. P. (2014) · Tissue Barriers · doi:10.4161/tisb.29528 · Cited by 338 · see citing works
Zi, Y., Yang, K., He, J., Wu, Z., Liu, J., & Zhang, W. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114449 · Cited by 268 · see citing works
Palanisamy, S., & Wang, Y.-M. (2019) · Dalton Transactions · doi:10.1039/c9dt00459a · Cited by 230 · see citing works
Non-genetic engineering of cells for drug delivery and cell-based therapy
Wang, Q., Cheng, H., Peng, H., Zhou, H., Li, P. Y., & Langer, R. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.12.003 · Cited by 225 · see citing works
Mofijur, M., Ahmed, S. F., Rahman, S. M. A., Arafat Siddiki, S. Y., Islam, A. B. M. S., Shahabuddin, M., Ong, H. C., Mahlia, T. M. I., Djavanroodi, F., & Show, P. L. (2021) · Environmental Research · doi:10.1016/j.envres.2021.110857 · Cited by 172 · see citing works
Nanocrystals: a perspective on translational research and clinical studies
Jarvis, M., Krishnan, V., & Mitragotri, S. (2019) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10122 · Cited by 162 · see citing works
Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Ferreira, R., Napoli, J., Enver, T., Bernardino, L., & Ferreira, L. (2020) · Nature Communications · doi:10.1038/s41467-020-18042-2 · Cited by 138 · see citing works
Ebrahim Attia, A. B., Yang, C., Tan, J. P. K., Gao, S., Williams, D. F., Hedrick, J. L., & Yang, Y.-Y. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.01.042 · Cited by 131 · see citing works
Liu, B., Han, L., Liu, J., Han, S., Chen, Z., & Jiang, L. (2017) · International Journal of Nanomedicine · doi:10.2147/ijn.s115136 · Cited by 129 · see citing works
Liu, L., Yi, H., He, H., Pan, H., Cai, L., & Ma, Y. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.04.043 · Cited by 124 · see citing works
Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles
Chuan, J., Li, Y., Yang, L., Sun, X., Zhang, Q., Gong, T., & Zhang, Z. (2013) · Journal of Nanoparticle Research · doi:10.1007/s11051-013-1634-1 · Cited by 107 · see citing works
Peptide-modified vemurafenib-loaded liposomes for targeted inhibition of melanoma via the skin
Zou, L., Ding, W., Zhang, Y., Cheng, S., Li, F., Ruan, R., Wei, P., & Qiu, B. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.08.013 · Cited by 92 · see citing works
Datta, N. R., Krishnan, S., Speiser, D. E., Neufeld, E., Kuster, N., Bodis, S., & Hofmann, H. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.09.016 · Cited by 92 · see citing works
Luiz, M. T., Abriata, J. P., Raspantini, G. L., Tofani, L. B., Fumagalli, F., de Melo, S. M. G., Emery, F. D. S., Swiech, K., Marcato, P. D., Lee, R., et al. (2019) · Materials Science and Engineering: C · doi:10.1016/j.msec.2019.110038 · Cited by 63 · see citing works
Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model
Vu, M. N., Rajasekhar, P., Poole, D. P., Khor, S. Y., Truong, N. P., Nowell, C. J., Quinn, J. F., Whittaker, M., Veldhuis, N. A., & Davis, T. P. (2019) · ACS Applied Nano Materials · doi:10.1021/acsanm.8b02056 · Cited by 52 · see citing works
Chen, K., Guo, L., Zhang, J., Chen, Q., Wang, K., Li, C., Li, W., Qiao, M., Zhao, X., Hu, H., et al. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.004 · Cited by 37 · see citing works
Microfluidic co-culture devices to assess penetration of nanoparticles into cancer cell mass
Jarvis, M., Arnold, M., Ott, J., Pant, K., Prabhakarpandian, B., & Mitragotri, S. (2017) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10079 · Cited by 32 · see citing works
Miele, D., Catenacci, L., Sorrenti, M., Rossi, S., Sandri, G., Malavasi, L., Dacarro, G., Ferrari, F., & Bonferoni, M. C. (2019) · Marine Drugs · doi:10.3390/md17090515 · Cited by 23 · see citing works
Stewart, M., Mulenos, M. R., Steele, L. R., & Sayes, C. M. (2018) · Applied Sciences · doi:10.3390/app8122669 · Cited by 21 · see citing works
- Authors
- He, C., Hu, Y., Yin, L., Tang, C., & Yin, C.
- Affiliations
- Fudan University (CN)
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 31
- Issue
- 13
- Pages
- 3657-3666
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2078057254
- Cited by
- 2,607
- References
- 36
- Citations by year
- 2026: 120 · 2025: 181 · 2024: 157 · 2023: 189 · 2022: 176 · 2021: 198 · 2020: 234 · 2019: 216 · 2018: 227 · 2017: 208 · 2016: 191 · 2015: 161 · 2014: 126 · 2013: 101 · 2012: 74
- FWCI
- 29.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30772656)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- polymeric nanoparticles, particle size, surface charge, cellular uptake, tissue distribution, chitosan, carboxymethyl chitosan, chitosan hydrochloride, protamine sulfate, camptothecin, rhodamine B, zeta potential, macrophage phagocytosis, tumor accumulation, drug nanocarriers, nanoparticle drug delivery
- MeSH terms
- Animals, Cell Line, Humans, Macrophages, Neoplasms, Experimental, Particle Size, Polymers, Surface Properties, Tissue Distribution, Mice, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
