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: The majority of anticancer drugs have poor aqueous solubility, produce adverse effects in healthy tissue, and thus impose major limitations on both clinical efficacy and therapeutic safety of cancer chemotherapy.

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These polymer-based prodrugs are macromolecular carriers, designed to increase the aqueous solubility of antitumor drugs, can enhance bioavailability.

Additionally, polymer-based prodrugs approach exploits unique features of tumor physiology to passively facilitate intratumoral accumulation, and so improve chemodrug pharmacokinetics and pharmacological properties.

This review introduces basic concepts of polymer-based prodrugs, provides an overview of currently emerging synthetic, natural, and genetically engineered polymers that now deliver anticancer drugs in preclinical or clinical trials, and highlights their major anticipated applications in anticancer therapies.

Cancer is one of the major fatal diseases, with current treatments of limited therapeutic efficacy, despite great progress in a range of approaches to tumor eradication, including chemotherapy.

The mechanism of action of anti-cancer drugs relies on arresting the cell cycle and rapidly killing all proliferating cells.

This killing includes non-cancerous cells, such as bone marrow, gut epithelia, lymphatic system, red blood cells and hair follicles.

One of the main challenges in current chemotherapeutic treatments is drug toxicity to healthy organs due to lack of selectivity.

To achieve therapeutic efficacy, it is often necessary to administer high doses of drugs because of the drugs’ physicochemical properties, such as short circulation time in the blood plasma.

The problems associated with the low specificity and poor pharmacokinetics and pharmacodynamics of chemotherapeutic drugs are well known; however, another frequently encountered difficulty is their poor aqueous solubility, which restricts bioavailability.

Intractable problems besetting drug solubility in aqueous solutions have imposed serious clinical constraints on ascertaining effective therapeutic plasma concentrations so as to achieve appropriately targeted pharmacological responses.

At present, ensuring the presence of a therapeutic concentration of poorly soluble drugs in systemic circulation requires the administration of high concentrations of potent chemotherapeutics, with their solubility related to particle size.

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