Challenges towards Targeted Drug Delivery in Cancer Nanomedicines

Abstract

Despite cancer nanomedicine celebrates already thirty years since its introduction, together with the achievements and progress in cancer treatment area, it still undergoes serious disadvantages that must be addressed. Since the first observation that macromolecules tend to accumulate in tumor tissue due to fenestrated endothelial of vasculature, considered as the “royal gate” in drug delivery field, more than dozens of nanoformulations have been approved and introduced into the practice for cancer treatment. Lipid, polymeric, and hybrid nanocarriers are biocompatible nano-drug delivery systems (NDDs) having suitable physicochemical properties and modulate payload release in response to specific chemical or physical stimuli. Biopharmaceutical properties of NDDs and their efficacy in animal models and humans can significantly affect their impact and perspective in nanomedicine. One of the future directions could be focusing on personalized cancer treatment, considering the heterogeneity and complexity of each patient tumor tissue and the designing of multifunctional targeted NDDs combining synthetic nanomaterials and biological components, like cellular membranes, circulating proteins, RNAi/DNAi, which enforce the efficacy of NDDs and boost their therapeutic effect.

Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model

“…The solution was then decanted, and the residue was washed with diethyl ether (2 × 10 mL) and dried overnight, under vacuum, originating bipy-PLA-OH polymer (white foam) with 82-95 % yield (Table 1). 1 To a stirred and degassed solution of bipy-PLA-OH (0.16 mmol) in a dichloromethane (10 mL)/DMF (3 mL) mixture, 5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno [3,4-d] imidazole-4-yl]pentanoic acid (biotin) (0.10 g, 0.4 mmol), 4-dimethylamino-pyridine (DMAP) (0.02 g, 0.16 mmol) and N-(3-dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride (EDC) (0.08 g, 0.4 mmol) were added. The esterification reaction was followed by 1 H-NMR spectroscopy until the terminal signal (HA') of the PLA chain completely disappeared.…”

“…The residue was washed with diethyl ether (2 × 10 mL) and dried overnight, under vacuum, originating L1 (white foam) with 90 % yield (Table 2). 1 (40 mL), L1 (L1_PLA1: 0.57 g, L1_PLA2: 0.18 mmol; L1_PLA1: 0.35 g, 0.08 mmol; L1_PLA3: 0.30 g, 0.08 mmol and 0.23 g, 0.05 mmol for 1, 2, 3 and 4, respectively) and AgCF 3 SO 3 (0.07 g, 0.27 mmol; 0.03 g, 0.12 mmol; 0.03 g, 0.12 mmol and 0.02 g, 0.08 mmol for 1, 2, 3 and 4, respectively) were added. After a 14, 19, 16 or 7 h reflux (for 1, 2, 3 or 4, respectively) the reaction mixture was cooled down to room temperature, filtered and the solvent was removed under vacuum.…”

“…Breast cancer is among the most common diseases, whereas triple negative breast cancer still lacks effective treatments. One of the key challenges in the treatment of cancer lies in engineering drug delivery systems capable of specifically and efficiently targeting the diseased cells without affecting healthy cells/tissues [1][2][3][4]. This might be achievable using a multi-targeting approach that is able to enhance the presence of the drug in tumor tissues with target-specific and localized action.…”

Recent Developments in Metallic Nanomaterials for Cancer Therapy, Diagnosing and Imaging Applications

“…Whether based on polymeric, liposomal, or metallic formulations, NPs naturally traffic to the spleen and lymph organs, being good candidates for delivering immunotherapeutic agents [8]. Moreover, nanomaterials can be used as cytotoxics and/or enhancers of standard chemotherapies, diminishing the side effects associated with conventional drugs, extending their blood circulation time, and preventing drug degradation before reaching the target site [1,10].…”

“…Pharmaceutics 2022, 14, x FOR PEER REVIEW 2 of 31 drugs, extending their blood circulation time, and preventing drug degradation before reaching the target site [1,10].…”