A novel mitochondrial targeted hybrid peptide modified HPMA copolymers for breast cancer metastasis suppression

Li, Qiuyi; Yang, Jiatao; Chen, Cheng; Lin, Xi; Zhou, Minglu; Zhou, Zhou; Huang, Yuan

doi:10.1016/j.jconrel.2020.06.010

Cited by 42 publications

(24 citation statements)

References 63 publications

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“…[ 9 ] In parallel, mitochondria in the cancer cell function as the powerhouse and vigorously provide energy to promote tumor proliferation and metastasis. [ 10 ] Hence, in addition to altering the tumor hypoxia, simultaneously interfering CAFs and mitochondria exhibit unique advantages to further suppress metastasis.…”

Section: Introductionmentioning

confidence: 99%

Sequentially Targeting Cancer‐Associated Fibroblast and Mitochondria Alleviates Tumor Hypoxia and Inhibits Cancer Metastasis by Preventing “Soil” Formation and “Seed” Dissemination

Yan

et al. 2021

Adv Funct Materials

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Tumor metastasis is facilitated by the formation of the premetastatic niche (PMN) in destination organs and the dissemination of cancer cells detached from a primary tumor. This study reports a sequential combination strategy that exerts a profound anti‐metastasis effect by inhibiting both PMN formation and cancer cell dissemination. The approach consists of (1) cancer‐associated fibroblast cells (CAFs)‐targeting liposome and (2) mitochondria‐targeting polymer. The liposome depletes CAFs and reduces tumor stroma, leading to a significant increase in intratumoral oxygen perfusion. The polymer disrupts mitochondria aerobic respiration in cancer cells, leading to a considerable decrease in intratumoral oxygen consumption. With the complementary mechanisms, their combination drastically alleviates the hypoxia in orthotopic breast tumor and inhibits the pulmonary PMN formation by downregulating various hypoxia‐induced PMN‐fostering factors. In addition, the CAFs depletion by the liposome abrogates the metastasis‐promoting crosstalk with cancer cells; meanwhile, mitochondria dysfunction by the polymer cuts off the energy supply that supports metastasis, together resulting in an efficient suppression of cancer cell dissemination. With the two‐pronged strategy targeting these two aspects, the primary tumor is prominently inhibited, and distant metastasis is completely eradicated. This study provides a generalizable approach of sequential CAFs depletion and mitochondria disruption to combat metastatic tumors.

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Section: Introductionmentioning

confidence: 99%

Sequentially Targeting Cancer‐Associated Fibroblast and Mitochondria Alleviates Tumor Hypoxia and Inhibits Cancer Metastasis by Preventing “Soil” Formation and “Seed” Dissemination

Yan

et al. 2021

Adv Funct Materials

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“…Emerging evidences showed that mitochondria played crucial roles in tumor metastasis. [ 53 ] They can provide energy for cell detachment from primary tumor to blood circulation, and participate in multiple metastasis‐associated pathways. Moreover, recent studies reported that enormous ROS generation could suppress distant tumor metastasis.…”

Section: Resultsmentioning

confidence: 99%

Stimuli‐Responsive Nanoparticles Combining Photodynamic Therapy and Mitochondria Disruption Suppressed Tumor Metastasis

Zhou

Yang

et al. 2021

Adv Materials Inter

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therapy (PDT) is an efficient noninvasive treatment modality that has attracted tremendous attention recently. By locally exposing photosensitizers to an appropriate wavelength laser, PDT can generate reactive oxygen species (ROS) which are irreversibly deleterious against tumor growth. Moreover, different from conventional chemotherapy, PDT rarely causes cancer cell resistance. [3,4] Nevertheless, PDT is the oxygen (O 2 )-dependent treatment that requires O 2 consumption to produce ROS. [5,6] Primary tumors with metastatic potential are typically advanced tumors where high levels of hypoxic stress exist. It has been well-documented that hypoxia in tumor microenvironment not only accelerates tumor invasion and migration, but also severely limits the efficacy of PDT. [7,8] Thus, a paramount point of applying PDT to metastatic tumor is to alleviate tumor hypoxia.

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“…Metastasis is a major challenge for TNBC treatment [40]. 4T1 breast tumor-bearing mice treated with the combination of two-steps MW irradiation with HA-BNPs@Ptx exhibited a reduction in spontaneous lung metastasis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Zhang

Gao

et al. 2021

Preprint

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Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very few treatment options. Although tumor-targeted nanomedicines hold great promise for the treatment of TNBC, the tumor microenvironment (TME) continues to be a major cause of failure in nanotherapy and immunotherapy. To overcome this barrier, we designed a new synergistic cascade strategy (SCS) that uses mild hyperthermia and smart drug delivery system (SDDS) to alter TME resistance in order to improve drug delivery and therapeutic efficacy of TNBC.Methods: Mild hyperthermia was produced by microwave (MW) irradiation. SDDS were formulated with thermosensitive polymer-lipid nanoparticles (HA-BNPs@Ptx), composed of polymer PLGA, phospholipid DPPC, hyaluronic acid (HA, a differentiation-44 targeted molecule, also known as CD44), 1-butyl-3-methylimidazolium-L-lactate (BML, a MW sensitizer) and paclitaxel (Ptx, chemotherapy drug). 4T1 breast tumor-bearing mice were treated with two-step MW combined with HA-BNPs@Ptx. Tumors in mice were pretreated with 1st MW irradiation prior to nanoparticle injection to modify TME and promote TME and promoting nanoparticle uptake and retention. The 2nd MW irradiation was performed on the tumor 24 h after the injection HA-BNPs@Ptx to produce a synergistic cascade effect through activating BML, thus enhancing hyperthermia effect, and instantly releasing Ptx at the tumor site.Results: Multifunctional CD44-targeted nanoparticles HA-BNPs@Ptx were successfully prepared and validated in-vitro. After the 1st MW irradiation of tumors in mice, the intratumoral perfusion increased by 2 times and the nanoparticle uptake augmented by 7 times. With the 2nd MW irradiation, remarkable anti-tumor effects were obtained with the inhibition rate up to 88%. In addition, immunohistochemical analysis showed that SCS therapy could not only promote the tumor cells apoptosis, trigger the immune response of cytotoxic T lymphocytes, but also significantly reduce the lung metastasis. Conclusions: The SCS using mild hyperthermia combined with smart drug delivery system, can significantly improve the efficacy of TNBC treatment in mice by modifying TME and hyperthermia-mediated EPR effects.

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A novel mitochondrial targeted hybrid peptide modified HPMA copolymers for breast cancer metastasis suppression

Cited by 42 publications

References 63 publications

Sequentially Targeting Cancer‐Associated Fibroblast and Mitochondria Alleviates Tumor Hypoxia and Inhibits Cancer Metastasis by Preventing “Soil” Formation and “Seed” Dissemination

Sequentially Targeting Cancer‐Associated Fibroblast and Mitochondria Alleviates Tumor Hypoxia and Inhibits Cancer Metastasis by Preventing “Soil” Formation and “Seed” Dissemination

Stimuli‐Responsive Nanoparticles Combining Photodynamic Therapy and Mitochondria Disruption Suppressed Tumor Metastasis

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

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