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Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells.

In recent years, multifunctional nanoparticles have received considerable attention in many applications such as biosensors, diagnostic nanoprobes and targeted drug delivery.[1] These efforts have been driven to a large extent by the need to improve biological specificity in diagnosis and therapy through the precise, spatio-temporal control of agent delivery. In order to achieve this goal, continuous efforts have been dedicated to develop stimuli-responsive nanoplatforms.[2] Environmental stimuli that were exploited include pH,[3] temperature,[4] enzymatic expression,[5] redox reaction[6] and light induction.[7] Among these activating signals, pH trigger is one of the most extensively studied stimuli based on two types of pH differences: (a) pathological (e.g. tumor) vs. normal tissues and (b) acidic intracellular compartments.[8] For example, due to the unusual acidity of the tumor extracellular microenvironment (pHe ≈ 6.5), several pHe-responsive nanosystems were reported to increase the sensitivity of tumor imaging or the efficacy of therapy.[9]