Intratumoral drug delivery (IT) is an inherently appealing approach for concentrating toxic
chemotherapies at the site of action. However, for most
chemotherapies, poor
tumor penetration and short retention at the administration site limit their anti-
tumor effects. In this work, we describe permeable nanoparticles (NPs) prepared with a novel amphiphilic
polymer, RRR-α-tocopheryl
succinate-grafted-ε-
polylysine conjugate (VES-g-ε-PLL). The nanoparticles (NPs) of VES-g-ε-PLL exhibited an ultra-small hydrodynamic diameter (20.8 nm) and positive zeta potential (20.6 mV), which facilitate strong
glioma spheroid penetration ability in vitro. Additionally, the hydrophobic model drug
docetaxel (DTX) could be effectively encapsulated in the nanoparticles with 3.99% drug loading and 73.37% encapsulation efficiency. To prolong the retention time of DTX-loaded nanoparticles (DTX-NPs) in the
tumor, intact decellularized brain extracellular matrix (dBECM) derived from healthy rats was used as a drug depot to adsorb the ultra-small DTX-NPs. The intact DTX-NPs-adsorbing dBECM scaffold was further homogenized into an
injectable DTX-NPs-dBECM
suspension for intratumoral administration. The DTX-NPs-dBECM
suspension exhibited slower DTX release than naked DTX-NPs without compromising the
tumor penetration ability of DTX-NPs. An antitumor study showed that the DTX-NPs-dBECM
suspension exhibited more powerful in vitro inhibition of
tumor spheroid growth than free DTX
solution or DTX-NPs. Due to strong
tumor penetration ability and prolonged retention, DTX-NPs-dBECM led to complete suppression of
glioma growth in vivo at 28 days
after treatment. The therapeutic mechanism was due to enhanced proliferation inhibition and apoptosis of
tumor cells and angiogenesis inhibition of
glioma after treatment with DTX-NPs-dBECM. Finally, the safety of DTX-NPs-dBECM at the therapeutic dose was demonstrated via pathological HE assay from heart, liver, spleen, lung and kidney tissues. In conclusion, permeable nanoparticle-absorbing dBECM is a potential carrier for intratumoral delivery of common chemotherapeutics.