Versatile Red Blood Cells for Triple‐Negative Breast Cancer Treatment via Stepwise Photoactivations

Abstract

Phototherapies have many advantages for triple-negative breast cancer (TNBC) treatment. However, their effects are often limited by short blood circulation time, poor tumor selectivity and weak penetration of phototherapeutic agents, and tumor hypoxia. For overcoming these limitations, a versatile biomimetic system is developed based on red blood cells (RBCs). Photothermal agent new indocyanine green (IR820) is conjugated with the cell/tissue-penetrating TAT peptide and further efficiently encapsulated into the intact RBCs by crossing cell membranes to realize the long blood circulation. Meanwhile, cyclic RGD peptide (cRGD) is linked to the surfaces of RBCs through phospholipid insertion to obtain tumor vessel-targeting ability. Photosensitizer temoporfin (mTHPC) is next loaded into the membranes of RBCs by spontaneous transferring. The acquired biomimetic system (cRGD-RBC@mTHPC/TAT-IR820) exhibits potent photodynamic performance upon 652 nm laser irradiation with the facilitation of oxyhemoglobin, which could not only trigger TAT-IR820 release but also destroy tumor vessels. TAT-IR820 penetrates deeply into tumor tissue via the mediation of TAT peptide, exerting greatly promoted photothermal ablation against TNBC upon 808 nm laser irradiation. In situ generated tumor antigens further induce robust immune responses to suppress TNBC recurrence and metastasis. In summary, this study provides a versatile biomimetic system for comprehensive TNBC treatment via stepwise photodynamic and photothermal activations.

RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions

“…It is a dangerous subtype with few therapeutic choices and a dismal prognosis. Integrins αvβ3, αvβ5, and α5β1 are widely overexpressed in TNBC, 195,196 and their interaction with RGD peptides has been studied for targeted drug delivery, imaging, and treatment 197–200 . MDA‐MB‐231 is a breast cancer cell line generated from a patient with triple‐negative/basal‐like breast cancer, which is distinguished by the lack of ER, PR, and HER2 expression and has a poor prognosis.…”

“…Integrins αvβ3, αvβ5, and α5β1 are widely overexpressed in TNBC, 195 , 196 and their interaction with RGD peptides has been studied for targeted drug delivery, imaging, and treatment. 197 , 198 , 199 , 200 MDA‐MB‐231 is a breast cancer cell line generated from a patient with triple‐negative/basal‐like breast cancer, which is distinguished by the lack of ER, PR, and HER2 expression and has a poor prognosis. Another breast cancer cell line produced by a patient with triple‐negative/basal‐like breast cancer is MDA‐MB‐468.…”

A biomimetic phototherapeutic nanoagent based on bacterial double-layered membrane vesicles for comprehensive treatment of oral squamous cell carcinoma

“…Bone marrow-derived DCs (BMDCs) were extracted from the normal mice for evaluating the immunostimulation effects of tumor-associated antigens and DAMPs released from SCC-7 cells with various treatments after 48 hour incubation. As the co-stimulatory molecules CD80/CD86 are the surface maturation markers of DCs, 41 we assessed the maturation of BMDCs through detecting the expression levels of CD80/CD86 after immunofluorescence staining with anti-CD11c, anti-CD80 and anti-CD86 antibodies. The results of flow cytometry are shown in Fig.…”

Glycopolymeric Photoactive Micelles for Glucose Transporter-Targeted Synergistic Combination Therapy

“…6 In addition, the strong absorption of porphyrin derivatives in the near-infrared region (NIR) (600−800 nm, red to dark red) and their higher photochemical stability make such PSs prominent. 7 Temoporfin, 8,9 porfimer sodium, 10 verteporfin, 11,12 redaporfin, 13 and 5-aminolevulinic acid (ALA), 14−16 PS agents have been widely used in clinical practice. Protoporphyrin IX (PpIX), a well-known PS for PDT, is a naturally occurring porphyrin component of hemoglobin, cytochrome c, and other biological molecules.…”

“…In addition, the strong absorption of porphyrin derivatives in the near-infrared region (NIR) (600–800 nm, red to dark red) and their higher photochemical stability make such PSs prominent . Temoporfin, , porfimer sodium, verteporfin, , redaporfin, and 5-aminolevulinic acid (ALA), − PS agents have been widely used in clinical practice.…”