Normalizing Tumor Blood Vessels to Improve Chemotherapy and Inhibit Breast Cancer Metastasis by Multifunctional Nanoparticles

Abstract

The abnormal tumor blood vessels with high leakage can promote tumor cells to infiltrate into the systemic circulation and increase the risk of tumor metastasis. In addition, chemotherapy may destroy tumor blood vessels and further aggravate metastasis. Normalizing tumor blood vessels can reduce vascular leakage and increase vascular integrity. The simultaneous administration of vascular normalization drugs and chemotherapy drugs may resist the blood vessels’ destruction of chemotherapy. Here, multifunctional nanoparticles (CCM@LMSN/DOX&St), which combined chemotherapy with tumor blood vessel normalization, were prepared for the treatment of breast cancer. The results showed that CCM@LMSN/DOX&St-loaded sunitinib (St) promoted the expression of junction proteins Claudin-4 and VE-cadherin of endothelial cells, reversed the destruction of DOX to the endothelial cell layer, protected the integrity of the endothelial cell layer, and inhibited the migration of 4T1 tumor cells across the endothelial cell layer. In vivo experiments showed that CCM@LMSN/DOX&St effectively inhibited tumor growth in situ; what is exciting was that it also inhibited distal metastasis of breast cancer. CCM@LMSN/DOX&St encapsulated with St can normalize tumor blood vessels, reverse the damage of DOX to tumor blood vessels, increase the integrity of blood vessels, and prevent tumor cell invasion into blood vessels, which can inhibit breast cancer spontaneous metastasis and reduce chemotherapy-induced metastasis. This drug delivery platform effectively inhibited the progression of tumors and provided a promising solution for effective tumor treatment.

Nomogram for Predicting Post-progression-free Survival in Patients with Recurrent Pancreatic Ductal Adenocarcinoma after Radical Surgery

“…The preceding research declared that chemotherapy inhibited tumor progression and metastasis [37][38][39][40] . Moreover, the overall survival of PDAC patients who received AG and Fol rinox schema was 6.8 and 11 months, respectively.…”

Tumor Cell Lysate-Based Multifunctional Nanoparticles Facilitate Enhanced mRNA Delivery and Immune Stimulation for Melanoma Gene Therapy

“…The Cell Counting Kit-8 (CCK-8) (Solarbio, Beijing, China) assay was employed to assess the in vitro cytotoxicity of the MLSV system. In brief, HEK 293T cells were incubated in 96-well plates at a density of 5 × 10 3 cells overnight. − Various concentrations of MLSV and DMP were added, with PEI25K used as the standard control for 24 h. Then, the CCK-8 agent was added to the cells to detect cytotoxicity at 450 nm.…”

The potential of vascular normalization for sensitization to radiotherapy

“…It is the theory of tumor vascular normalization that raises the clinical status of anti-angiogenic therapy, while with the development of nanotechnology, the application of nanocarriers provides more possibilities for corresponding anti-angiogenic therapy, and provides a theoretical basis for finding more appropriate anti-tumor combination therapy, marking the arrival of the era of induced tumor vascular normalization [ 18 , 20 ]. For example, the vascular normalization “time window” provides an opportunity for tumor chemotherapy, effectively prevents the development of drug resistance, and promotes the development of anti-angiogenic drugs [ 21 ]. Nanocarrier delivery of STING agonists also enhances tumor immunotherapy [ 22 ].…”