Rapid cut‐off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half‐lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane‐camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt‐PA), to local thrombus sites. The tailor‐designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt‐PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt‐PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.
Compared
with traditional chemotherapeutics, vascular disruption
agents (VDAs) have the advantages of rapidly blocking the supply of
nutrients and starving tumors to death. Although the VDAs are effective
under certain scenarios, this treatment triggers angiogenesis in the
later stage of therapy that frequently leads to tumor recurrence and
treatment failure. Additionally, the nonspecific tumor targeting and
considerable side effects also impede the clinical applications of
VDAs. Here we develop a customized strategy that combines a VDA with
an anti-angiogenic drug (AAD) using mesoporous silica nanoparticles
(MSNs) coated with platelet membrane for the self-assembled tumor
targeting accumulation. The tailor-made nanoparticles accumulate in
tumor tissues through the targeted adhesion of platelet membrane surface
to damaged vessel sites, resulting in significant vascular disruption
and efficient anti-angiogenesis in animal models. This study demonstrates
the promising potential of combining VDA and AAD in a single nanoplatform
for tumor eradication.
To better make nanomedicine entering the clinic, developing new rationally designed nanotherapeutics with a deeper understanding of tumor biology is required. The tumor microenvironment is similar to the inflammatory response in a healing wound, the milieu of which promotes tumor cell invasion and metastasis. Successful targeting of the microenvironmental components with effective nanotherapeutics to modulate the tumor microvessels or restore the homeostatic mechanisms in the tumor stroma will offer new hope for cancer treatment. We here highlight the progress in constructing nanotherapeutics to target or modulate the tumor microenvironment. We discuss the factors necessary for nanomedicines to become a new paradigm in cancer therapy, including the selection of drugs and therapeutic targets, controllable synthesis, and tempo-spatial drug release. K E Y W O R D S drug delivery, nanotherapeutics, therapeutic targets, tumor microenvironment Guangjun Nie and Suping Li are co-corresponding authors.Yinlong Zhang and Shih-Hsin Ho contributed equally to this work.
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