Photoimmunotherapy with cetuximab-conjugated gold nanorods reduces drug resistance in triple negative breast cancer spheroids with enhanced infiltration of tumor-associated macrophages

Emami, Fakhrossadat; Pathak, Shiva; Nguyen, Tiep Tien; Shrestha, Prakash; Maharjan, Srijan; Kim, Jong Oh; Jeong, Jee–Heon; Yook, Simmyung

doi:10.1016/j.jconrel.2020.10.001

Cited by 40 publications

(36 citation statements)

References 99 publications

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“…Despite poor prognosis of TNBC with only a small number of known actionable biomarkers, cytotoxic chemotherapy remains the most influential treatment in the neoadjuvant, adjuvant, and metastatic settings [ 6 , 15 ]. While patients with other subtypes of BC display a lower response to chemotherapy, patients with TNBC experience a higher likelihood of responding to chemotherapy, but this anticipatory response to chemotherapy is accompanied by a high risk of recurrence [ 6 , 15 ] notably earlier than other subtypes [ 16 ]; this phenomenon is referred to as the TNBC paradox [ 15 ]. Standard pre-operative regimens for TNBC that have resulted in the most considerable improvement in pCR include anthracyclines such as doxorubicin (adriamycin, DOX) or epirubicin, alkylating agents such as cyclophosphamide, and members of the taxane family.…”

Section: Current Strategies For Tnbc Treatmentmentioning

confidence: 99%

“…The 60–70% of patients with TNBC who do not achieve complete response to chemotherapy would benefit from personalized and tumor-specific molecular targeting therapies because of tumor heterogeneity. Approximately 90% of patients with TNBC with persisting sickness after chemotherapy can benefit from drugs targeting different molecular pathways, including the PARP and PI3K inhibitors [ 6 , 15 ]. According to a retrospective analysis, neoadjuvant regimens consisting of taxane and anthracycline resulted in a pCR rate as high as 52% in patients presenting with BL1 tumors, whereas the lowest pCR rates, with 0%, 10%, and 23% in patients with BL2, LAR, and MSL tumor types, respectively [ 15 ].…”

Section: Current Strategies For Tnbc Treatmentmentioning

confidence: 99%

“…Different varieties of NPs have been developed to improve their anti-cancer efficacy through the enhanced permeability and retention (EPR) effect and targeted therapy of cancer [ 6 , 28 , 29 ]; however, most exogenous NPs synthesized using organic or inorganic materials are immunogenic [ 6 , 30 ]. These exogenous NPs are rapidly cleared by the reticuloendothelial system (RES), and exhibit long-term toxicity, poor biodegradation, and low bioavailability [ 31 ].…”

Section: Bio-inspired Tumor-homing Nanosystems For Tnbc Treatmentmentioning

confidence: 99%

“…The term triple negative breast cancer (TNBC) stands for a subtype of BC that is negative for the HER2 amplification, and both ER and PR expression [ 4 ]. TNBC is a type of BC that is not sensitive to current hormone-based chemotherapies or anti-HER2 treatments [ 5 , 6 ]. In addition, other characteristics of TNBC include a dense extracellular matrix and an increased tumor interstitial fluid pressure (IFP), both of which cause insufficient cancer cell internalization and deep interstitial penetration [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the initial chemosensitivity of TNBC as compared with other types of BC, a high risk of recurrence in patients not achieving pathological complete response (pCR) exists [ 13 ]. Treatment re-challenging in recurrent or metastatic TNBC is the only available strategy because of multiple limiting factors such as a poor objective response, multi-drug resistance, and unacceptable toxicity, which all require an urgent need to targeted therapy [ 6 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Bio-Inspired and Smart Nanoparticles for Triple Negative Breast Cancer Microenvironment

et al. 2021

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Triple negative breast cancer (TNBC) with poor prognosis and aggressive nature accounts for 10–20% of all invasive breast cancer (BC) cases and is detected in as much as 15% of individuals diagnosed with BC. Currently, due to the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor, there is no hormone-based therapy for TNBC. In addition, there are still no FDA-approved targeted therapies for patients with TNBC. TNBC treatment is challenging owing to poor prognosis, tumor heterogeneity, chemotherapeutic side effects, the chance of metastasis, and multiple drug-resistance. Therefore, various bio-inspired tumor-homing nano systems responding to intra- and extra- cellular stimuli are an urgent need to treat TNBC patients who do not respond to current chemotherapy. In this review, intensive efforts have been made for exploring cell-membrane coated nanoparticles and immune cell-targeted nanoparticles (immunotherapy) to modulate the tumor microenvironment and deliver accurate amounts of therapeutic agents to TNBC without stimulating the immune system.

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Section: Current Strategies For Tnbc Treatmentmentioning

confidence: 99%

Section: Current Strategies For Tnbc Treatmentmentioning

confidence: 99%

Section: Bio-inspired Tumor-homing Nanosystems For Tnbc Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bio-Inspired and Smart Nanoparticles for Triple Negative Breast Cancer Microenvironment

et al. 2021

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A Mitochondria‐Targeted Ferroptosis Inducer Activated by Glutathione‐Responsive Imaging and Depletion for Triple Negative Breast Cancer Theranostics

Gan

Huang

Luo

et al. 2023

Adv Healthcare Materials

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Ferroptosis is a new type of iron‐dependent programmed cell death characterized by glutathione (GSH) depletion, selenoprotein glutathione peroxidase 4 (GPX4) inactivation, and lipid peroxides accumulation. Mitochondria, as the main source of intracellular energy supply and reactive oxygen species (ROS) generation, play a central role in oxidative phosphorylation and redox homeostasis. Therefore, targeting cancer‐cell mitochondria and attacking redox homeostasis is expected to induce robust ferroptosis‐mediated anticancer effects. In this work, a theranostic ferroptosis inducer (IR780‐SPhF), which can simultaneously achieve the imaging and therapy of triple‐negative breast cancer (TNBC) by targeting mitochondria is presented. It is developed from a mitochondria‐targeting small molecule (IR780) with cancer‐preferential accumulation, enabling it to react with GSH by nucleophilic substitution, resulting in mitochondrial GSH depletion and redox imbalance. More interestingly, IR780‐SPhF exhibits GSH‐responsive near‐infrared fluorescence emission and photoacoustic imaging characteristics, further facilitating diagnosis and treatment with real‐time monitoring of TNBC with a highly elevated GSH level. Both in vitro and in vivo results demonstrate that IR780‐SPhF exhibits potent anticancer effect, which is significantly stronger than cyclophosphamide, a classic drug commonly recommended for TNBC patients in clinic. Hence, the reported mitochondria‐targeted ferroptosis inducer may represent a promising candidate and a prospective strategy for efficient cancer treatment.

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Two‐pronged reversal of chemotherapy resistance by gold nanorods induced mild photothermal effect

Shang,

Chen,

et al. 2024

Bioengineering & Transla Med

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Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross‐resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid‐labile hydrazone bond. Stimulated by the acidic media in endocytic organelles, DOX@FG exhibited a responsive dissociation for the controlled release of chemotherapeutic DOX. Surprisingly, we found the mild photothermal effect elicited by GNRs under NIR irradiation simultaneously inhibited the pump and nonpump resistance mechanisms, enhancing the intracellular DOX accumulation and sensitizing the cancer cells to DOX, collectively amplify the chemotherapy efficacy and delay the MCF‐7/ADR breast tumor growth. This intelligent DOX@FG nanomedicine with the potential for two‐pronged reversal of MDR may provide a prospective way to encourage chemotherapy efficacy.

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Photoimmunotherapy with cetuximab-conjugated gold nanorods reduces drug resistance in triple negative breast cancer spheroids with enhanced infiltration of tumor-associated macrophages

Cited by 40 publications

References 99 publications

Bio-Inspired and Smart Nanoparticles for Triple Negative Breast Cancer Microenvironment

Bio-Inspired and Smart Nanoparticles for Triple Negative Breast Cancer Microenvironment

A Mitochondria‐Targeted Ferroptosis Inducer Activated by Glutathione‐Responsive Imaging and Depletion for Triple Negative Breast Cancer Theranostics

Two‐pronged reversal of chemotherapy resistance by gold nanorods induced mild photothermal effect

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