Recent advances in long-acting drug delivery systems for anticancer drug

Pacheco, Catarina; Baião, Ana; Ding, Tao; Cui, Wenguo; Sarmento, Bruno

doi:10.1016/j.addr.2023.114724

“…To further improve the antitumor efficiency of 1f , targeted delivery systems for 1f were constructed. Herein, based on the homologous targeting ability and biocompatibility of tumor cell membrane and albumin, , two drug delivery systems (DDS), i.e., low-drug-loading (LDL) carrier and high-drug-loading (HDL) carrier, were developed (Scheme ). Initially, for 1f @BSA, the core of BSA was exposed using the disulfide bond-reducing method, and the addition of 1f caused its self-assembly to form albumin-based NPs (Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Reprogramming Energy Metabolism with Synthesized PDK Inhibitors Based on Dichloroacetate Derivatives and Targeted Delivery Systems for Enhanced Cancer Therapy

She,

Liu,

Li

et al. 2023

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In many types of cancers, pyruvate dehydrogenase kinase (PDK) is abnormally overexpressed and has become a promising target for cancer therapy. However, few highly effective inhibitors of PDK have been reported to date. Herein, we designed and synthesized a series of PDK inhibitors based on dichloroacetate (DCA) and arsenicals. Of the 27 compounds, 1f demonstrated PDK inhibition with high efficiency at a cellular level (IC 50 = 2.0 μM) and an enzyme level (EC 50 = 68 nM), far more effective than that of DCA. In silico, in vitro, and in vivo studies demonstrated that 1f inhibited PDK, shifted the energy metabolism from aerobic glycolysis to oxidative phosphorylation, and induced cell apoptosis. Moreover, new 1f-loaded nanoparticles were developed, and the administration of high-drug-loading nanoparticles (0.15 mg/kg) caused up to 90% tumor shrinkage without any apparent toxicity. Hence, this study provided a novel metabolic therapy for cancer treatment.

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“…It becomes more complicated after including tumorigenesis, metastasis, and immune evasion, as stated in our previous paper [32]. Chemoresistance develops over time, limiting clinical application and raising concerns about efficacy and systemic toxicity [33][34]. Many attempts intend to solve this problem, but none combines CuZn into a biosensor to stimulate drug release for OS therapy [30] [35].…”

Section: Introductionmentioning

confidence: 99%

“…Our efforts to develop a multifunctional biosensor for OS therapy (OST), however, will be insufficient unless we investigate the physiological functions of CuZn [37]. On the contrary, not much research on CuZn has successfully provided details of multifunctional biosensors for balancing and controlling drug release during cancer invasion [34]. Despite this, their chelation structures [38], aromatic organic solvents [39], and donor atoms of ligands [18] remain unclear, making structural strength [40] the primary barrier to therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi¹,

Miskon²

2023

Preprint

0

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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“…This problem increases after long-term treatments due to its acquired and accumulated nature [ 30 , 31 ]. Chemoresistance develops over time, limiting clinical application and raising concerns about efficacy and systemic toxicity [ 32 , 33 ]. Many attempts intend to solve this problem, but none combine CuZn into a biosensor to stimulate drug release for OS therapy (OST) [ 30 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Our efforts to develop a multifunctional biosensor for OST, however, will be insufficient unless we investigate the physiological functions of CuZn [ 36 ]. On the contrary, not much research on CuZn has successfully provided details of multifunctional biosensors for balancing and controlling drug release during cancer invasion [ 33 ]. Despite this, their chelation structures [ 37 ], aromatic organic solvents [ 38 ], and donor atoms of ligands [ 18 ] remain unclear, making structural strength [ 39 ] the primary barrier to therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi

¹

,

Miskon

²

2023

Molecules

17

0

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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Recent advances in long-acting drug delivery systems for anticancer drug

Cited by 75 publications

References 127 publications

Reprogramming Energy Metabolism with Synthesized PDK Inhibitors Based on Dichloroacetate Derivatives and Targeted Delivery Systems for Enhanced Cancer Therapy

Reprogramming Energy Metabolism with Synthesized PDK Inhibitors Based on Dichloroacetate Derivatives and Targeted Delivery Systems for Enhanced Cancer Therapy

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

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