Scheme 1

a Schematic illustration of construction of multi-pocket nanoparticles. b Elucidation of in vivo drug delivery of DOX-loaded MPNs. (i) A large supramolecular structure and PEGylation of MPNs prolong their blood circulation time; (ii) Prolonged circulation facilitates accumulation of large MPNs at tumor sites via the EPR effect; (iii) Shrinkage of MPNs into small-sized nanoparticles in tumor extracellular acidic environment is favourable for deep tumor penetration. (C) Cleavage of disulfide linkages and subsequent disintegration of small nanoparticles in an intracellular reductive environment lead to DOX release into cytoplasm and nucleus