Biochemical hallmarks-targeting antineoplastic nanotherapeutics
Source abstract
Abstract
Tumor microenvironments (TMEs) have received increasing attention in recent years as they play pivotal roles in tumorigenesis, progression, metastases, and resistance to the traditional modalities of cancer therapy like chemotherapy. With the rapid development of nanotechnology, effective antineoplastic nanotherapeutics targeting the aberrant hallmarks of TMEs have been proposed. The appropriate design and fabrication endow nanomedicines with the abilities for active targeting, TMEs-responsiveness, and optimization of physicochemical properties of tumors, thereby overcoming transport barriers and significantly improving antineoplastic therapeutic benefits. This review begins with the origins and characteristics of TMEs and discusses the latest strategies for modulating the TMEs by focusing on the regulation of biochemical microenvironments, such as tumor acidosis, hypoxia, and dysregulated metabolism. Finally, this review summarizes the challenges in the development of smart anti-cancer nanotherapeutics for TME modulation and examines the promising strategies for combination therapies with traditional treatments for further clinical translation.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Nanoplatforms for cancer theranostics · Cancer, Hypoxia, and Metabolism · Enzyme function and inhibition
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 201010.1016/S0140-6736(12)61728-0 ↗
2. Prodrug-based nanoparticulate drug delivery strategies for cancer therapy10.1016/j.tips.2014.09.008 ↗
3. Cancer nanomedicine: Progress, challenges and opportunities10.1038/nrc.2016.108 ↗
4. Nanotechnology for boosting cancer immunotherapy and remodeling tumor microenvironment: The horizons in cancer treatment10.1021/acsnano.1c02103 ↗
5. Polyprodrug nanomedicines: An emerging paradigm for cancer therapy10.1002/adma.202107434 ↗
6. An in situ nanoparticle recombinant strategy for the enhancement of photothermal therapy10.1016/j.cclet.2021.07.025 ↗
7. A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours10.3109/1061186X.2016.1154561 ↗
8. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin10.1016/j.jconrel.2016.04.028 ↗
9. Obstacles and opportunities in a forward vision for cancer nanomedicine10.1038/s41563-021-01047-7 ↗
10. Targeting tumor microenvironment for cancer therapy10.3390/ijms20040840 ↗
11. Role of tumor microenvironment in tumorigenesis10.7150/jca.17648 ↗
12. Overview on clinical relevance of intra-tumor heterogeneity10.3389/fmed.2018.00085 ↗
13. Extracellular cell matrix stiffness-driven drug resistance of breast cancer cells via EGFR activation10.1016/j.mbm.2023.100023 ↗
14. Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer10.1016/j.biomaterials.2022.121599 ↗
15. Multi-stimuli-responsive and cell membrane camouflaged aggregation-induced emission nanogels for precise chemo-photothermal synergistic therapy of tumors10.1021/acsnano.3c08409 ↗
16. A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia- triggered differentiation therapy10.1016/j.apsb.2022.05.027 ↗
17. Dual hypoxia-responsive supramolecular complex for cancer target therapy10.1038/s41467-023-41388-2 ↗
18. Stimuli-responsive polymer-based nanosystems for cancer theranostics10.1021/acsnano.3c06019 ↗
19. Interfering with pH regulation in tumours as a therapeutic strategy10.1038/nrd3554 ↗
20. Warburg effect in colorectal cancer: The emerging roles in tumor microenvironment and therapeutic implications10.1186/s13045-022-01358-5 ↗
21. Cancer metabolism: A therapeutic perspective10.1038/nrclinonc.2016.60 ↗
22. Structural basis of human monocarboxylate transporter 1 inhibition by anti-cancer drug candidates10.1016/j.cell.2020.11.043 ↗
23. Prolyl hydroxylase 2: A promising target to inhibit hypoxia-induced cellular metabolism in cancer cells10.1016/j.drudis.2018.05.016 ↗
24. Roos · Physiol. Rev. · 1981 · 61 · 29610.1152/physrev.1981.61.2.296 ↗
25. Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies10.1080/14756360902784425 ↗
26. Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression10.1016/j.semcancer.2008.03.011 ↗
27. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
28. Proton dynamics in cancer10.1186/1479-5876-8-57 ↗
29. Cancer-associated, hypoxia-inducible carbonic anhydrase IX facilitates CO2 diffusion10.1111/j.1464-410X.2008.07644.x ↗
30. Hypoxia signalling in cancer and approaches to enforce tumour regression10.1038/nature04871 ↗
31. Tumor-associated carbonic anhydrase 9 spatially coordinates intracellular pH in three-dimensional multicellular growths10.1074/jbc.M801330200 ↗
32. Tumor cell metabolism: Cancer’s Achilles’ heel10.1016/j.ccr.2008.05.005 ↗
33. Extracellular acidity as favouring factor of tumor progression and metastatic dissemination
34. A hierarchical structured fiber device remodeling the acidic tumor microenvironment for enhanced cancer immunotherapy10.1002/adma.202300216 ↗
35. Tumor-microenvironment-activatable polymer nano-immunomodulator for orecision cancer photoimmunotherapy10.1002/adma.202106654 ↗
36. The potential role of systemic buffers in reducing intratumoral extracellular pH and acid-mediated invasion10.1158/0008-5472.CAN-08-2394 ↗
37. Systemic buffers in cancer therapy: The example of sodium bicarbonate; stupid idea or wise remedy?10.4172/2161-0444.1000314 ↗
38. Enhancement of chemotherapy by manipulation of tumour pH10.1038/sj.bjc.6690455 ↗
39. Bicarbonate increases tumor pH and inhibits spontaneous metastases10.1158/0008-5472.CAN-07-5575 ↗
40. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: An integrative modelling study10.1038/bjc.2012.58 ↗
41. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment10.1038/s41565-018-0319-4 ↗
42. Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo10.1039/C5NR06162H ↗
43. Multifunctional albumin-MnO2 nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response10.1021/nn405773r ↗
44. Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin10.1016/j.jconrel.2019.01.004 ↗
45. Chemical modulation of glucose metabolism with a fluorinated CaCO3 nanoregulator can potentiate radiotherapy by programming antitumor immunity10.1021/acsnano.2c02688 ↗
46. Coordination polymer-coated CaCO3 reinforces radiotherapy by reprogramming the immunosuppressive metabolic microenvironment10.1002/adma.202106520 ↗
47. CaCO3-encapuslated microspheres for enhanced transhepatic arterial embolization treatment of hepatocellular carcinoma10.1002/adhm.202100748 ↗
48. Tumor microenvironment modulating CaCO3-based colloidosomal microreactors can generally reinforce cancer immunotherapy10.1002/adma.202308254 ↗
49. Drug-incorporating calcium carbonate nanoparticles for a new delivery system10.1016/j.jconrel.2004.11.015 ↗
50. The inhibition of human bladder cancer growth by calcium carbonate/CaIP6 nanocomposite particles delivering AIB1 siRNA10.1016/j.biomaterials.2012.09.068 ↗
51. Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis10.2217/nnm-2018-0302 ↗
52. Why do cancers have high aerobic glycolysis?10.1038/nrc1478 ↗
53. Tumour hypoxia induces a metabolic shift causing acidosis: A common feature in cancer10.1111/j.1582-4934.2009.00994.x ↗
54. Multifunctional albumin-MnO2 nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response10.1021/nn405773r ↗
55. Nanoscale CaH2 materials for synergistic hydrogen-immune cancer therapy10.1016/j.chempr.2021.11.020 ↗
56. Efficient immunotherapy of drug-free layered double hydroxide nanoparticles via neutralizing excess acid and blocking tumor cell autophagy10.1021/acsnano.2c02183 ↗
57. Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics10.1158/1535-7163.MCT-06-0024 ↗
58. Acidic extracellular microenvironment and cancer10.1186/1475-2867-13-89 ↗
59. Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro10.1016/S0006-2952(03)00467-2 ↗
60. Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain10.1016/j.bbamem.2015.02.004 ↗
61. Drug resistance and cellular adaptation to tumor acidic pH microenvironment10.1021/mp200292c ↗
62. On the origin of cancer cells10.1126/science.123.3191.309 ↗
63. The monocarboxylate transporter family--Structure and functional characterization10.1002/iub.573 ↗
64. Hallmarks of cancer: The next generation10.1016/j.cell.2011.02.013 ↗
65. Hexokinase-2 bound to mitochondria: Cancer’s stygian link to the “Warburg Effect” and a pivotal target for effective therapy10.1016/j.semcancer.2008.11.006 ↗
66. Targeting VDAC-bound hexokinase II: A promising approach for concomitant anti-cancer therapy10.1517/14728222.2013.833607 ↗
67. Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 210.1186/s13046-017-0530-4 ↗
68. Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer10.4161/cc.26461 ↗
69. Investigating metformin for cancer prevention and treatment: The end of the beginning10.1158/2159-8290.CD-12-0263 ↗
70. Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II10.1038/srep02070 ↗
71. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro10.4161/cc.8.6.7933 ↗
72. Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration10.1038/srep17423 ↗
73. Targeting cancer cell metabolism: The combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells10.1158/0008-5472.CAN-09-2782 ↗
74. Single cell "glucose nanosensor" verifies elevated glucose levels in individual cancer cells10.1021/acs.nanolett.5b04495 ↗
75. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer10.1002/jcp.20166 ↗
76. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways10.1172/JCI63146 ↗
77. Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells10.18632/oncotarget.2892 ↗
78. Metabolic targets for cancer therapy10.1038/nrd4145 ↗
79. Targeting cellular metabolism to improve cancer therapeutics10.1038/cddis.2013.60 ↗
80. Targeting glucose uptake with siRNA-based nanomedicine for cancer therapy10.1016/j.biomaterials.2015.01.068 ↗
81. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo10.1158/1535-7163.MCT-12-0131 ↗
82. Overcoming the heat endurance of tumor cells by interfering with the anaerobic glycolysis metabolism for improved photothermal therapy10.1021/acsnano.6b06658 ↗
83. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes10.1158/0008-5472.CAN-11-1272 ↗
84. Inhibitory effect of tumor cell-derived lactic acid on human T cells10.1182/blood-2006-07-035972 ↗
85. Regulatory circuits of T cell function in cancer10.1038/nri.2016.80 ↗
86. Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation10.1016/j.semcancer.2017.03.001 ↗
87. Neutralization of tumor acidity Improves antitumor responses to immunotherapy10.1158/0008-5472.CAN-15-1743 ↗
88. Obstacles posed by the tumor microenvironment to T cell activity: A case for synergistic therapies10.1016/j.ccell.2017.02.008 ↗
89. Coordinated regulation of myeloid cells by tumours10.1038/nri3175 ↗
90. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments10.1016/j.cmet.2016.12.018 ↗
91. Nanoenabled modulation of acidic tumor microenvironment reverses anergy of infiltrating T cells and potentiates anti-PD-1 therapy10.1021/acs.nanolett.8b04296 ↗
92. Reprogramming tumor immune microenvironment (TIME) and metabolism via biomimetic targeting codelivery of shikonin/JQ110.1021/acs.nanolett.9b00021 ↗
93. Pharmacological properties of shikonin - A review of literature since 200210.1055/s-0033-1350934 ↗
94. Shikonin-enhanced cell immunogenicity of tumor vaccine is mediated by the differential effects of DAMP components10.1186/s12943-015-0435-9 ↗
95. Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA110.18632/oncotarget.9660 ↗
96. BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression10.1016/j.celrep.2016.08.032 ↗
97. Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer10.1158/2159-8290.CD-16-1020 ↗
98. BET bromodomain inhibition cooperates with PD-1 blockade to facilitate antitumor response in Kras-mutant non-small cell Lung cancer10.1158/2326-6066.CIR-18-0077 ↗
99. Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles
100. A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole10.1016/j.colsurfb.2013.06.035 ↗