Nanoparticle-Loaded Polarized-Macrophages for Enhanced Tumor Targeting and Cell-Chemotherapy
Corresponding Author: Na Zhang
Nano-Micro Letters,
Vol. 13 (2021), Article Number: 6
Abstract
Cell therapy is a promising strategy for cancer therapy. However, its therapeutic efficiency remains limited due to the complex and immunosuppressive nature of tumor microenvironments. In this study, the “cell-chemotherapy” strategy was presented to enhance antitumor efficacy. M1-type macrophages, which are therapeutic immune cells with both of immunotherapeutic ability and targeting ability, carried sorafenib (SF)-loaded lipid nanoparticles (M1/SLNPs) were developed. M1-type macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver SF to tumor tissues for chemotherapy simultaneously. M1-type macrophages were obtained by polarizing macrophages using lipopolysaccharide, and M1/SLNPs were obtained by incubating M1-type macrophages with SLNP. Tumor accumulation of M1/SLNP was increased compared with SLNP (p < 0.01), which proved M1/SLNP could enhance tumor targeting of SF. An increased ratio of M1-type macrophages to M2-type macrophages, and the CD3+CD4+ T cells and CD3+CD8+ T cell quantities in tumor tissues after treatment with M1/SLNP indicated M1/SLNP could relieve the immunosuppressive tumor microenvironments. The tumor volumes in the M1/SLNP group were significantly smaller than those in the SLNP group (p < 0.01), indicating M1/SLNP exhibited enhanced antitumor efficacy. Consequently, M1/SLNP showed great potential as a novel cell-chemotherapeutic strategy combining both cell therapy and targeting chemotherapy.
Highlights:
1 A polarized-macrophages-based drug delivery system (M1/SLNP) was presented for the cell-chemotherapy of cancer.
2 Polarized-macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver chemotherapeutic drugs to tumor tissues for chemotherapy simultaneously.
3 M1/SLNP was a multifunctional delivery system with simple structure, excellent safety, and without complex synthesis process.
Keywords
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- J.H. Oved, D.M. BarrettD.T. Teachey, Cellular therapy: immune-related complications. Immunol. Rev. 290, 114–126 (2019). https://doi.org/10.1111/imr.12768
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- S.B. Lee, J.-E. Lee, S.J. Cho, J. Chin, S.K. Kim et al., Crushed gold shell nanoparticles labeled with radioactive iodine as a theranostic nanoplatform for macrophage-mediated photothermal therapy. Nano-Micro Lett. 11, 240–253 (2019). https://doi.org/10.1007/s40820-019-0266-0
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References
J.H. Oved, D.M. BarrettD.T. Teachey, Cellular therapy: immune-related complications. Immunol. Rev. 290, 114–126 (2019). https://doi.org/10.1111/imr.12768
K. Rezvani, Adoptive cell therapy using engineered natural killer cells. Bone Marrow Transpl. 54, 785–788 (2019). https://doi.org/10.1038/s41409-019-0601-6
S. Lee, S. Kivimäe, A. Dolor, F.C. Szoka, Macrophage-based cell therapies: the long and winding road. J. Control. Rel. 240, 527–540 (2016). https://doi.org/10.1016/j.jconrel.2016.07.018
M.A. Fischbach, J.A. BluestoneW.A. Lim, Cell-based therapeutics: the next pillar of medicine. Sci. Transl. Med. 5, 1797 (2013). https://doi.org/10.1126/scitranslmed.3005568
S.R. Riddell, D. Sommermeyer, C. Berger, L.S. Liu, A. Balakrishnan et al., Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. Cancer J. 20, 141–144 (2014). https://doi.org/10.1097/PPO.0000000000000036
J. Tang, V.M. Hubbard-Lucey, L. Pearce, J. O'Donnell-Tormey, A. Shalabi, The global landscape of cancer cell therapy. Nat. Rev. Drug Discov. 17, 465–466 (2018). https://doi.org/10.1038/nrd.2018.74
M.M. D'Aloia, I.G. Zizzari, B. Sacchetti, L. PierelliM, Alimandi, CAR-T cells: the long and winding road to solid tumors. Cell Death Dis. 9, 282 (2018). https://doi.org/10.1038/s41419-018-0278-6
I. Scarfò, M.V. Maus, Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment. J. Immunother. Cancer 5, 28 (2017). https://doi.org/10.1186/s40425-017-0230-9
R. Elahi, E. Khosh, S. Tahmasebi, A. Esmaeilzadeh, Immune cell hacking: challenges and clinical approaches to create smarter generations of chimeric antigen receptor T cells. Front. Immunol. 9, 1717 (2018). https://doi.org/10.3389/fimmu.2018.01717
J.A. Figueroa, A. Reidy, L. Mirandola, K. Trotter, N. Suvorava et al., Chimeric antigen receptor engineering: a right step in the evolution of adoptive cellular immunotherapy. Inter. Rev. Immunol. 34, 154–187 (2015). https://doi.org/10.3109/08830185.2015.1018419
L. Ma, T. Dichwalkar, J.Y.H. Chang, B. Cossette, D. Garafola et al., Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science 365, 162–168 (2019). https://doi.org/10.1126/science.aav8692
L. Shen, H. Li, S. Bin, P. Li, J. Chen et al., The efficacy of third generation anti-HER2 chimeric antigen receptor T cells in combination with PD1 blockade against malignant glioblastoma cells. Oncol. Rep. (2019). https://doi.org/10.3892/or.2019.7263
F. Zhang, N.N. Parayath, C.I. Ene, S.B. Stephan, A.L. Koehne et al., Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nat. Commun. 10, 3974–3974 (2019). https://doi.org/10.1038/s41467-019-11911-5
R. Noy, J.W. Pollard, Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014). https://doi.org/10.1016/j.immuni.2014.06.010
J. Conde, C. Bao, Y. Tan, D. Cui, E.R. Edelman et al., Dual targeted immunotherapy via in vivo delivery of biohybrid RNAi-peptide nanoparticles to tumour-associated macrophages and cancer cells. Adv. Funct. Mater. 25, 4183–4194 (2015). https://doi.org/10.1002/adfm.201501283
D. Saha, R.L. Martuza, S.D. Rabkin, Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade. Cancer Cell 32, 253.e5–267.e5 (2017). https://doi.org/10.1016/j.ccell.2017.07.006
M. Yang, D. McKay, J.W. PollardC.E. Lewis, Diverse functions of macrophages in different tumor microenvironments. Cancer Res. 78, 5492–5503 (2018). https://doi.org/10.1158/0008-5472.CAN-18-1367
C. Ngambenjawong, H.H. GustafsonS.H. Pun, Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Del. Rev. 114, 206–221 (2017). https://doi.org/10.1016/j.addr.2017.04.010
T.Q. Wang, J. Zhang, T. Hou, X.L. YinN, Zhang, Selective targeting of tumor cells and tumor associated macrophages separately by twin-like core-shell nanoparticles for enhanced tumor-localized chemoimmunotherapy. Nanoscale 11, 13934–13946 (2019). https://doi.org/10.1039/C9NR03374B
W. Zhang, L. Liu, H. Su, Q. Liu, J. Shen et al., Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix. Br. J. Cancer 121, 837–845 (2019). https://doi.org/10.1038/s41416-019-0578-3
C. Varol, A. MildnerS, Jung, Macrophages: development and tissue specialization. Annu. Rev. Immunol. 33, 643–675 (2015). https://doi.org/10.1146/annurev-immunol-032414-112220
H. Zhao, L. Li, J. Zhang, C. Zheng, K. Ding et al., C-C chemokine ligand 2 (CCL2) recruits macrophage-membrane-camouflaged hollow bismuth selenide nanoparticles to facilitate photothermal sensitivity and inhibit lung metastasis of breast cancer. ACS Appl. Mater. Interfaces 10, 31124–31135 (2018). https://doi.org/10.1021/acsami.8b11645
N. Linde, M. Casanova-Acebes, M.S. Sosa, A. Mortha, A. Rahman et al., Macrophages orchestrate breast cancer early dissemination and metastasis. Nat. Commun. 9, 21–21 (2018). https://doi.org/10.1038/s41467-017-02481-5
F. Geissmann, M.G. Manz, S. Jung, M.H. Sieweke, M. Merad et al., Development of monocytes, macrophages, and dendritic cells. Science 327, 656–661 (2010). https://doi.org/10.1126/science.1178331
Z. Li, H. Huang, S. Tang, Y. Li, X.-F. Yu et al., Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy. Biomaterials 74, 144–154 (2016). https://doi.org/10.1016/j.biomaterials.2015.09.038
S. Banskota, P. YousefpourA, Chilkoti, Cell-based biohybrid drug delivery systems: the best of the synthetic and natural worlds. Macromol. Biosci. 17, 1600361 (2017). https://doi.org/10.1002/mabi.201600361
X. He, H. Cao, H. Wang, T. Tan, H. Yu et al., Inflammatory monocytes loading protease-sensitive nanoparticles enable lung metastasis targeting and intelligent drug release for anti-metastasis therapy. Nano Lett. 17, 5546–5554 (2017). https://doi.org/10.1021/acs.nanolett.7b02330
M.A. Evans, P.-J. Huang, Y. Iwamoto, K.N. Ibsen, E.M. Chan et al., Macrophage-mediated delivery of light activated nitric oxide prodrugs with spatial, temporal and concentration control. Chem. Sci. 9, 3729–3741 (2018). https://doi.org/10.1039/C8SC00015H
X. Gong, J. Li, T. Tan, Z. WangY, Li, Emerging Approaches of cell-based nanosystems to target cancer metastasis. Adv. Funct. Mater. 29, 1–36 (2019). https://doi.org/10.1002/adfm.201903441
S.B. Lee, J.-E. Lee, S.J. Cho, J. Chin, S.K. Kim et al., Crushed gold shell nanoparticles labeled with radioactive iodine as a theranostic nanoplatform for macrophage-mediated photothermal therapy. Nano-Micro Lett. 11, 240–253 (2019). https://doi.org/10.1007/s40820-019-0266-0
J. Fu, D. Wang, D. Mei, H. Zhang, Z. Wang et al., Macrophage mediated biomimetic delivery system for the treatment of lung metastasis of breast cancer. J. Control. Rel. 204, 11–19 (2015). https://doi.org/10.1016/j.jconrel.2015.01.039
L. An, Y. Wang, J. Lin, Q. Tian, Y. Xie et al., Macrophages-mediated delivery of small gold nanorods for tumor hypoxia photoacoustic imaging and enhanced photothermal therapy. ACS Appl. Mater. Interfaces 11, 15251–15261 (2019). https://doi.org/10.1021/acsami.9b00495
L. Pang, J. Qin, L. Han, W. Zhao, J. Liang et al., Exploiting macrophages as targeted carrier to guide nanoparticles into glioma. Oncotarget 7, 37081–37091 (2016). https://doi.org/10.18632/oncotarget.9464
W. Zhang, M. Wang, W. Tang, R. Wen, S. Zhou et al., Nanoparticle-laden macrophages for tumor-tropic drug delivery. Adv. Mater. 30, e1805557 (2018). https://doi.org/10.1002/adma.201805557
Y. Hui, X. Yi, F. Hou, D. Wibowo, F. Zhang et al., Role of nanoparticle mechanical properties in cancer drug delivery. ACS Nano 13, 7410–7424 (2019). https://doi.org/10.1021/acsnano.9b03924
Y. Malam, M. LoizidouA.M. Seifalian, Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol. Sci. 30, 592–599 (2009). https://doi.org/10.1016/j.tips.2009.08.004
B. García-Pinel, C. Porras-Alcalá, A. Ortega-Rodríguez, F. Sarabia, J. Prados et al., Lipid-based nanoparticles: application and recent advances in cancer treatment. Nanomaterials 9, 638 (2019). https://doi.org/10.3390/nano9040638
J. Zhang, T.Q. Wang, S.J. Mu, L.D. Olerile, X.Y. Yu et al., Biomacromolecule/lipid hybrid nanoparticles for controlled delivery of sorafenib in targeting hepatocellular carcinoma therapy. Nanomedicine 12, 911–925 (2017). https://doi.org/10.2217/nnm-2016-0402
S.M. Hoy, Patisiran: first global approval. Drugs 78, 1625–1631 (2018). https://doi.org/10.1007/s40265-018-0983-6
A.-L. Cheng, Y.-K. Kang, Z. Chen, C.-J. Tsao, S. Qin et al., Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10, 25–34 (2009). https://doi.org/10.1016/S1470-2045(08)70285-7
R. Poojari, S. Kini, R. SrivastavaD, Panda, Intracellular interactions of electrostatically mediated layer-by-layer assembled polyelectrolytes based sorafenib nanoparticles in oral cancer cells. Colloid. Surfaces B 143, 131–138 (2016). https://doi.org/10.1016/j.colsurfb.2016.03.024
J.M. Llovet, R. Montal, D. SiaR.S. Finn, Molecular therapies and precision medicine for hepatocellular carcinoma: nature reviews. Clin. Oncol. 15, 599–616 (2018). https://doi.org/10.1038/s41571-018-0073-4
K.M. Gillian, Sorafenib: a review in hepatocellular carcinoma. Targeted Oncol. 12, 1–11 (2017). https://doi.org/10.1007/s11523-017-0484-7
S.L. Zhou, Z.J. Zhou, Z.Q. Hu, X.W. Huang, Z. Wang et al., Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology 150, 1646–1658.e17 (2016). https://doi.org/10.1053/j.gastro.2016.02.040
R. Zhang, Z. Chen, S.S. Wu, J. Xu, L.C. Kong et al., Celastrol enhances the anti-liver cancer activity of sorafenib. Med. Sci. Monitor 25, 4068–4075 (2019). https://doi.org/10.12659/MSM.914060
X. Tang, L. Chen, A. Li, S. Cai, Y. Zhang et al., Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma. Drug Deliv. 25, 1484–1494 (2018). https://doi.org/10.1080/10717544.2018.1477859
R.K. Thapa, J.Y. Choi, B.K. Poudel, T.T. Hiep, S. Pathak et al., Multilayer-coated liquid crystalline nanoparticles for effective sorafenib delivery to hepatocellular carcinoma. ACS Appl. Mater. Interfaces 7, 20360–20368 (2015). https://doi.org/10.1021/acsami.5b06203
X. Li, W. Yao, Y. Yuan, P. Chen, B. Li et al., Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut 66, 157–167 (2017). https://doi.org/10.1136/gutjnl-2015-310514