The Improved Antineoplastic Activity of Thermophilic L-Asparaginase Tli10209 via Site-Directed Mutagenesis.

Amino acid deprivation therapy (AADT) is a novel anticancer therapy, considered nontoxic and selective. Thermophilic L-asparaginase enzymes display high stability and activity at elevated temperatures. However, they are of limited use in clinical applications because of their low substrate affinity and reduced activity under physiological conditions, which may necessitate an improved dosage, leading to side effects and greater costs.

Selective enhanced cytotoxicity of amino acid deprivation for cancer therapy using thermozyme functionalized nanocatalyst.

Background: Enzyme therapy based on differential metabolism of cancer cells has demonstrated promising potential as a treatment strategy. Nevertheless, the therapeutic benefit of reported enzyme drugs is compromised by their uncontrollable activity and weak stability. Additionally, thermozymes with high thermal-stability suffer from low catalytic activity at body temperature, preventing them from functioning independently.

TfR Aptamer-Functionalized MSNs for Enhancing Targeted Cellular Uptake and Therapy of Cancer Cells.

Mesoporous silica nanoparticles (MSNs), as novel nanocarriers for drug delivery in cancer treatment, have attracted widespread concern because of their rich pore structure, large pore capacity, ease of modification, and biocompatibility. However, the limitation of nontargeting and low uptake efficiency hindered their further application. Considering the overexpression of the transferrin receptor (TfR) on most cancer cell membranes, herein, we propose a strategy to effectively enhance the cellular internalization of MSNs by arming them with the TfR aptamer.

Phenylboronic Acid-Modified Polyamidoamine Mediated the Transfection of Polo-Like Kinase-1 siRNA to Achieve an Anti-Tumor Efficacy.

Background: The construction of tumor-targeting carriers with favorable transfection efficiency was of great significance to achieve the tumor gene therapy. The phenylboronic acid-modified polyamidoamine (namely PP) was employed as a carrier for the delivery of Polo-like kinase-1 siRNA (siPlk-1), inducing an obvious anti-tumor response.

Materials And Methods: The interaction between PP and siPlk-1 was evaluated by gel retardation assay.

Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment.

Combination therapy based on the co-delivery of therapeutic genes and anti-cancer drugs has emerged as a promising approach in the cancer treatment, and stimuli-responsive delivery systems could further improve the therapeutic efficacy. Herein, an ATP aptamer and its complementary DNA were used to form Duplex into which doxorubicin (DOX) was loaded to construct DOX-Duplex, and then the lipoic acid-modified oligoethyleneimine (LA-OEI) was employed as a carrier to realize the co-delivery of DOX-Duplex and miR-23b. The ternary nanocomplex LA-OEI/miR-23b/DOX-Duplex showed excellent anti-proliferative effect by inducing the cell apoptosis via mitochondrial signaling pathway and arresting the cell cycle at S phase.

A genipin-crosslinked protein-polymer hybrid system for the intracellular delivery of ribonuclease A.

Background: Therapeutic proteins have been widely used in the treatment of various diseases, and effective carriers are highly required for achieving protein delivery to obtain favorable treatment potency.

Materials And Methods: A protein-polymer hybrid system was constructed through the genipin-mediated crosslinking of polyethyleneimine with a weight-average molecular weight of 25,000 g/mol (PEI25K) and ribonuclease A (RNase A), namely RGP.

Results: The RGP nanoparticles were observed to be easily internationalized in HeLa cells owing to the introduction of positively charged PEI25K, thereby triggering the antiproliferative effects by cleaving RNA molecules in the tumor cells.