Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

Pan, Yuan‐Bo; Tang, Wei; Fan, Wenpei; Zhang, Jianmin; Chen, Xiaoyuan

doi:10.1039/d1cs01145f

Cited by 34 publications

(21 citation statements)

References 757 publications

(1,016 reference statements)

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“…However, the challenges of normal tissue intolerance and suboptimal treatment effectiveness have driven significant interest in combination therapies. 102,103 Zhou reported a drug delivery strategy that combines radiotherapy with SNA nano-drugs. 104 The SNA structure played a dual role in enhancing radiotherapy and acting as an immunomodulator.…”

Section: Snas With External Energy Lightsmentioning

confidence: 99%

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms

Tao,

Zhang,

et al. 2024

Nanoscale

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Section: Snas With External Energy Lightsmentioning

confidence: 99%

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms

Tao,

Zhang,

et al. 2024

Nanoscale

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“…Hypoxia‐sensitive magnetic resonance imaging, positron‐emission tomography imaging, computed tomography imaging, photoacoustic imaging, and fluorescence imaging are clearly needed. [ 56 ]…”

Section: Remodeling the Tme To Overcome Radio‐resistancementioning

confidence: 99%

Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy

2023

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or intra-arterial administration of therapeutic radionuclides or by direct implantation of radioisotope-embedded beads into tumors. [3] In external RT, therapeutic doses of ionizing radiation are delivered to tumors using external beams of photo ns, electrons, and protons. [4] Both types of RT can directly induce local apoptosis, autophagy, necrosis, or replicative senescence of cancer cells [5] by producing reactive oxygen species (ROS) [6] to cause DNA damage. [7] Advances in hardware and software technologies have provided conformal radiation techniques, [8] which are aided by advanced imaging systems to deliver a desired dose of radiation to the precise location of a tumor, thus maximizing therapeutic effects while minimizing radiation damage to normal organs. [9] Radiosensitizers can be introduced during RT to enhance the radiotherapeutic effects of ionizing radiation. The radiosensitizers can be classified as: 1) chemotherapies such as cisplatin, 5-fluorouracil, and taxanes; 2) gaseous molecules such as O 2 , NO, and H 2 S; and 3) high-Z elements such as Au, Ba, Bi, Pt, Hf, and W. Chemotherapies presumably enhance RT by arresting cancer cells in the most radiation-sensitive phases of the cell cycle and eliminating radioresistant cells in late S phase but often cause debilitating side effects to cancer patients. Gaseous radiosensitizers enhance RT by increasing ROS production and/or reducing the expression of hypoxia-inducible factor-1α (HIF-1α). It is, however, challenging to ensure therapeutic efficacy due to the difficulty in controlling their concentrations, diffusion rates, and tumor retention. High-Z elements enhance RT by increasing biological reactions and depositing more radiation energy in tumors, via their stronger interactions with secondary photons and electrons, than in normal tissues. [10] In addition to increasing local antitumor effects of RT, the holy grail of radiosensitizer design is to improve the killing of tumor cells outside of the irradiated fields (abscopal effect). An ideal radiosensitizer would enhance RT to produce systemic antitumor effects by inducing immunogenic cell death (ICD), enhancing the presentation of tumor-associated antigens (TAAs), and activating cytotoxic T cells to mount host immune responses.Although RT is widely used to treat many different types of tumors, it has several limitations. First, radio-resistance is a key impediment to both curative and palliative RT. Previous research on enhancing the effectiveness of RT has mainly focused on cancer cells while neglecting the complicated Radiotherapy (RT) uses ionizing radiation to eradicate localized tumors and, in rare cases, control tumors outside of the irradiated fields via stimulating an antitumor immune response (abscopal effect). However, the therapeutic effect of RT is often limited by inherent physiological barriers of the tumor microenvironment (TME), such as hypoxia, abnormal vasculature, dense extracellular matrix (ECM), and an immunosuppressive TME. Thus, it is critical to develop new RT strategies tha...

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“…[ 11 ] In this way, calcium supplementation, in combination with ROS‐generating anti‐tumor treatments, may not only induce “calcium death” of tumor cells, but also strengthen the systemic anti‐tumor innate and adaptive immune response. [ 12 ] Since radiotherapy could produce abundant ROS in tumors while feebly induce antitumor immune response, [ 13 ] the regulation of H + and Ca 2+ homeostasis in tumor cells would provide benefits for radio‐immunotherapy. [ 14 ]…”

Section: Introductionmentioning

confidence: 99%

“…[11] In this way, calcium supplementation, in combination with ROS-generating anti-tumor treatments, may not only induce "calcium death" of tumor cells, but also strengthen the systemic anti-tumor innate and adaptive immune response. [12] Since radiotherapy could produce abundant ROS in tumors while feebly induce antitumor immune response, [13] the regulation of H + and Ca 2+ homeostasis in tumor cells would provide benefits for radio-immunotherapy. [14] In this study, we synthesized liposome-coated carbonic anhydrase inhibitor (CAI)-loaded calcium carbonate nanoparticles (CaCO 3 /CAI@Liposome (CCL)) as pH-responsive nanomedicine to reprogram the H + and Ca 2+ content inside and outside tumor cells for enhanced radio-immunotherapy (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Ion Homeostasis for Enhanced Tumor Radio‐Immunotherapy

Qian,

Yi,

Liu

et al. 2023

Advanced Science

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Intra/extracellular ion content affects the growth and metastasis of tumor cells, as well as the efficacy of various antitumor therapies. Herein, a carbonic anhydrase inhibitor (CAI) is loaded onto pH‐responsive calcium carbonate (CaCO3) nanoparticles and then modify theses nanoparticles with liposomes to obtain biocompatible CaCO3/CAI@Lipsome (CCL) for enhance tumor radio‐immunotherapy. CCL can specially decompose in tumor microenvironment, releasing calcium ion (Ca2+) and CAI, as well as increasing the pH value of extracellular fluid. CAI restrains the flow of hydrogen ion (H+) inside and outside the tumor cells, resulting in the reversal of tumor acidic microenvironment and the increase of intracellular H+, both of which can improve the sensitivity of tumor to radiotherapy. Afterward, the increased intracellular H+ together with radiotherapy‐causes reactive oxygen species promotes calcium influx, leading to cellular calcium overload. Moreover, the CCL‐tailored content of H+ and Ca2+ strengthens radiotherapy‐induced immunogenic cell death and dendritic cell maturation, amplifying systemic anti‐tumor adaptive immunity. Meanwhile, macrophages in the CCL‐treated tumors are polarized from pro‐tumor M2 to anti‐tumor M1 under X‐ray exposure, owing to the neutralization of tumor acidic microenvironment and enhances Ca2+ content. Therefore, multi‐directional regulation of the intra/extra tumor cell pH/calcium by simple nano‐preparation would provide a powerful way to improve the efficacy of radio‐immunotherapy.

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Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

Abstract: Radiotherapy (RT), including external beam RT and internal radiation therapy, uses high-energy ionizing radiation to kill tumor cells.

Cited by 34 publications

References 757 publications

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms

Spherical nucleic acids: emerging amplifiers for therapeutic nanoplatforms

Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy

Regulation of Ion Homeostasis for Enhanced Tumor Radio‐Immunotherapy

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