Tuning nanoparticle core composition drives orthogonal fluorescence amplification for enhanced tumour imaging.

Tumour detection with high selectivity and sensitivity is crucial for delineating tumour margins and identifying metastatic foci during image-guided surgery. Optical nanoprobes with preferential tumour accumulation is often limited by inefficient amplification of biological signals. Here, we report the design of a library of hydrophobic core-tunable ultra-pH-sensitive nanoprobes (HUNPs) for orthogonally amplifying tumour microenvironmental signals on multiple tumour models.

pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy.

Tumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging.

A pH-Responsive Nanoparticle Library with Precise pH Tunability by Co-Polymerization with Non-Ionizable Monomers.

Precise monitoring of the subtle pH fluctuation during biological events remains a big challenge. Previously, we reported an ultra-pH-sensitive (UPS) nanoprobe library with a sharp pH response using co-polymerization of two tertiary amine-containing monomers with distinct pK . Currently, we have generalized the UPS nanoparticle library with tunable pH transitions (pH ) by copolymerization of a tertiary amine-containing monomer with a series of non-ionizable monomers.

Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy.

Nanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions.