Abstract
A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the nanocarrier using a cathepsin B cleavable spacer: glycine–phenylalanine–leucine–glycine (GFLG). The in vitro analysis of the time-dependent drug release, binding and internalization ability, and the cytotoxic nature showed that this drug delivery system (DDS) is highly effective. The efficacy analysis using non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice also showed that compared to the control group, the DDS can effectively reduce tumor volume. The mice that received the DDS appeared to gain weight more rapidly than the free drug, which suggests that the dendrimer is more easily tolerated by mice than the free drug.
Highlights
Materials 2022, 15, 800. https://The International Agency for Research on Cancer (IARC), in December 2020, reported that breast cancer is the most commonly occurring cancer in the world
We proposed to design and synthesize a fourth generation lysine dendritic nanocarrier based on the concept put forward by Helmut Ringsdorf in 1975 to be utilized as a drug delivery agent to deliver MTX [16]
The advantage of targeted drug delivery in cancer using nanocarriers/nanoparticles over The conventional chemotherapy minimum maximum efficacy. This advantage of targetedincludes drug delivery in toxicity cancer and using nanocarriers/nanoparticles over conventional chemotherapy includes minimum toxicity and maximum efficacy. This could be the result of controlled drug release and improved pharmacokinetics and pharmacodynamics
Summary
The International Agency for Research on Cancer (IARC), in December 2020, reported that breast cancer is the most commonly occurring cancer in the world. According to the GLOBOCAN report, there were over 2.3 million cases and 685,000 deaths in the world in 2020 due to the fact of breast cancer. Chemotherapy is a better option for treating advanced breast cancers. The narrow therapeutic index of the anticancer drugs and several offtarget side effects associated with their biodistribution require further refinement to make it the best option for breast cancer treatment. Nanocarrier-based targeted drug delivery systems (DDS) provide enhanced selectivity, reduced drug-associated toxicity, improved drug solubility, and prolonged circulation in plasma [1]. Dendritic nanocarriers or dendrimers have gained wide attention over the past several years due to the fact of their high drug-loading capacity, low polydispersity, and high resistance to proteolytic degradation
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