Abstract

Polyamidoamine (PAMAM) dendrimers have gained so much attention for drug and gene delivery since they have
been introduced decades ago. The internal cavities and multivalent surface groups of PAMAM dendrimers have
been widely used for small-molecule drugs/biomacromolecules encapsulation and conjugation. The involvement
of PAMAM dendrimers in drug delivery systems (DDSs) has significantly improved drug pharmacokinetics and
enhanced drug accumulation in pathological sites. The recent progress has been made on the design of stimuli-
responsive PAMAM-based nano-sized vehicles that potentially deliver drugs in a spatially and/or temporally
controlled fashion. Such smart dendrimer nanocarriers further the efficiency of targeted drug delivery, while
decrease systemic exposure. In the review, we discuss recent advances in the design of PAMAM dendrimer-based
DDSs that are able to release carried therapeutics only in response to a specific endogenous and exogenous
stimuli.