Enhancing Apoptosome Assembly via Mito‐Biomimetic Lipid Nanocarrier for Cancer Therapy

Abstract

Apoptosis is the natural programmed cell death process, which is responsible for abnormal cell clearance. However, many cancer cells develop various mechanisms to escape apoptosis through interrupting apoptosome assembly, which is a key step to initiate apoptosis. This promotes tumorigenesis and drug resistance, and thus, poses a great challenge in cancer treatment. Herein, a biomimetic lipid nanocarrier mimicking mitochondrial Cytochrome C (Cyt C) binding is developed. Cardiolipin, the major phospholipid of mitochondrial inner membrane, is introduced as the main component in biomimetic liposomal formulation. With the help of cardiolipin, Cyt C is sufficiently loaded in liposome based on electrostatic and hydrophobic interaction with cardiolipin. Lonidamine (LND) is added in hydrophobic phase of liposome to modulate the metabolic activity within cancer cells and sensitize the cells to Cyt C‐induced apoptosis. The results suggest that LND reduces ATP level and creates favorable environment for Cyt C induced apoptosome assembly, exhibiting higher apoptosis level and anti‐tumor efficacy in vitro and in vivo. The conjugation of a tumor‐homing peptide, LinTT1, on the nanovesicle, increases the efficacy due to enhanced tumor accumulation. Overall, this biomimetic lipid nanocarrier proves to be an efficient delivery system with great potential of pro‐apoptosis cancer therapy.

Lipid nanoparticles-based RNA therapies for breast cancer treatment

“…As discussed above, the off-target effect associated with many nanomedicines remains a limitation that needs to be overcome, as it implies an increased dose of drug to achieve the desired therapeutic effect and reduces the bioavailability of the drug. Affinity targeting of the LNPs to the BC lesions can be easily achieved due to several chemical surface modifications [23,111]. By attaching smart molecules to the available functional groups of the lipids the selectivity and effectiveness can be certainly improved.…”

“…Source: GLOBOCAN 2022 [16] A more recent therapeutic approach is represented by immunotherapy. Cancer immunotherapy harnesses the body's own immune system to target tumor cells, with various approaches [23,24]; currently, a few of them are also exploited as BC treatment options [25]. These strategies include the use of monoclonal antibodies, immune checkpoint inhibitors, and vaccines designed to prime the immune system against cancer cells [26].…”