Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression

Abstract

Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression. nanomaterials | drug delivery | cancer therapy | microfluidics R ecent advances in cancer therapy development often demand the simultaneous delivery of multiple drugs that work in a synergistic manner (1-4). These drugs can vary in their chemical properties, further adding complexity to their encapsulation and delivery. Delivery systems can suffer from low loading efficiencies, particularly when combinations of both hydrophobic and hydrophilic drugs are required. Hydrophobic anticancer drugs face additional significant barriers to their use as they have low bioavailability and are rapidly eliminated from the body. In vivo, delivery of drug combinations (5, 6) requires specific, biodegradable vehicles to protect the therapeutics from the physiological environment and to guide and control their release (7-14). Additionally, stimuli-responsive treatments are increasingly widely used to complement drug-based therapy (15)(16)(17)(18)(19). For example, photothermal therapy promotes cell death using heat that is locally activated by near-infrared (NIR) radiation (20). However, it is challenging to integrate high drug-loading efficiency, the ability to coload multiple therapeutics, and stimuli responsiveness into a single carrier system. Carriers that move toward realizing these multipronged approaches to cancer therapy will push the frontiers of drug delivery and enable the development of new, more effective treatments.In this work, we sy...

The Construction and Application of Three‐Dimensional Biomaterials

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Current Advances of Hollow Capsules as Controlled Drug Delivery Systems

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Immunotherapeutic silk inverse opal particles for post-surgical tumor treatment

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