Layer-by-layer (LbL)-engineered nanoparticles (NPs) are a promising group of therapeutic carriers used in an increasing number of biomedical applications. The present study uses a controlled LbL process to create a multidrug-loaded nanoplatform capable of promoting blood circulation time, biodistribution profile and controlling drug release in the dynamic systemic environment. LbL assembly is achieved by sequential deposition of poly-L-lysine (PLL) and poly(ethylene glycol)-block-poly(L-aspartic acid) (PEG-b-PLD) on liposomal nanoparticles (LbL-LNPs). This generates spherical and stable multilayered NPs ∼240 nm in size, enabling effective systemic administration. The numerous functional groups and compartments in the polyelectrolyte shell and core facilitate loading with doxorubicin and mitoxantrone. The nanoarchitecture effectively controls burst release, providing different release kinetics for each drug. LbL-LNPs are pH-sensitive, indicating that intracellular drug release can be increased by the acidic milieu of cancer cells. We further demonstrate that the LbL nanoarchitecture significantly reduces the elimination rates of both drugs tested and markedly extends their systemic circulation times, paving the way for efficacious tumor drug delivery. Because this delivery system accommodates multiple drugs, improves drug half-life and diminishes burst release, it provides an exciting platform with remarkable potential for combination therapeutics in cancer therapy.
Bibliographical noteFunding Information:
This research was supported by a National Research Foundation of Korea ( NRF ) grant funded by the Ministry of Education, Science and Technology (No. 2012R1A2A2A02044997 and No. 2012R1A1A1039059 ).
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