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Tunable, ultra-pH responsive fluorescent nanoparticles with multichromatic emissions are highly valuable in a variety of biological studies, such as endocytic trafficking, endosome/lysosome maturation, and pH regulation in subcellular organelles. Small differences (e.g., <1 pH unit) and yet finely regulated physiological pH inside different endocytic(More)
CRISPR/Cas is a revolutionary gene editing technology with wide-ranging utility. The safe, non-viral delivery of CRISPR/Cas components would greatly improve future therapeutic utility. We report the synthesis and development of zwitterionic amino lipids (ZALs) that are uniquely able to (co)deliver long RNAs including Cas9 mRNA and sgRNAs. ZAL nanoparticle(More)
Stimuli-responsive nanomaterials are increasingly important in a variety of applications such as biosensing, molecular imaging, drug delivery and tissue engineering. For cancer detection, a paramount challenge still exists in search of methods that can illuminate tumors universally regardless of their genotypes and phenotypes. Here we capitalized on the(More)
Traditional micelle self-assembly is driven by the association of hydrophobic segments of amphiphilic molecules forming distinctive core-shell nanostructures in water. Here we report a surprising chaotropic-anion-induced micellization of cationic ammonium-containing block copolymers. The resulting micelle nanoparticle consists of a large number of ion pairs(More)
In recent years, multifunctional nanoparticles have received considerable attention in many applications such as biosensors, diagnostic nanoprobes, and targeted drug delivery. These efforts have been driven to a large extent by the need to improve biological specificity in diagnosis and therapy through the precise spatiotemporal control of agent delivery.(More)
The ability to control chemical functionality is an exciting feature of modern polymer science that enables precise design of drug delivery systems. Ring-opening polymerization of functional monomers has emerged as a versatile method to prepare clinically translatable degradable polyesters.1 A variety of functional groups have been introduced into lactones;(More)
Tremendous effort has been made to improve stability and delivery efficacy of small RNA therapeutics. However, nearly all current nano-encapsulation carriers utilize the critical balance between only two interacting parameters: RNA-binding electrostatic interactions and nanoparticle-stabilizing hydrophobic interactions. We report the development of(More)
The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest(More)
Breast cancer metastasis is the major cause of cancer death in women worldwide. Early detection would save many lives, but current fluorescence imaging probes are limited in their detection ability, particularly of bone and liver micrometastases. Herein, probes that are capable of imaging tiny (<1 mm) micrometastases in the liver, lung, pancreas, kidneys,(More)
Dysregulated pH has been recognized as a universal tumor microenvironment signature that can delineate tumors from normal tissues. Existing fluorescent probes that activate in response to pH are hindered by either fast clearance (in the case of small molecules) or high liver background emission (in the case of large particles). There remains a need to(More)