Natural gels are constrained by a limited number of building blocks, yet based on time and space organization, they perform diverse functions. In contrast, the properties of synthetic hydrogels are frequently tuned through substantial changes in their chemical make-up, causing complex interplay between composition, structure, and properties. This work fabricates a series of hydrogels with identical compositions but disparate properties by selectively quenching the depth and path of a water vapor-induced phase separation process. These hydrogels are solely comprised of short alkyl side-modified polyvinyl alcohol at the same volume fraction, but they exhibit hierarchical differences across multiple length scales, including porous morphology (≈µm), hydrophobic clusters (≈10 nm), and molecular packing (subnm). The hierarchical discrepancy is explicitly related to the striking contrast in terms of turbidity, permeability, stretchability, and viscoelasticity, thus advancing the understanding of the relationship between multiscale structures and properties without interference from chemical formulations. In addition, the hydrogels exhibit excellent biocompatibility, acid-aided degradability, in situ healability, and underwater malleability. This work exploits a design principle to imitate the hierarchically specific tenet in nature, that is, the spatiotemporal organization of a single type of polymer via kinetic arrest of network-forming phase separation, rather than modulation of the chemical make-ups.
Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.
Chemotherapy is a conventional cancer treatment in clinical settings. Although numerous nano drug delivery systems have been developed, the chemotherapeutic effect is greatly limited by abnormal tumor mechanics in solid...
Imaging-guided diagnosis and chemo-photothermal combinational therapy have promising application for the treatment of cancer. Nevertheless, the accurate diagnosis and efficient treatment of tumor is not yet satisfying. Herein, a tumor...
Over the past several decades, the importance of tumor mechanical microenvironment (TMME) in cancer progression and cancer therapy has been recognized by researchers world-wide. The abnormal mechanical properties of tumor...
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