TY - JOUR
T1 - Antitumor Therapeutics: A Virus‐Mimicking pH‐Responsive Acetalated Dextran‐Based Membrane‐Active Polymeric Nanoparticle for Intracellular Delivery of Antitumor Therapeutics (Adv. Funct. Mater. 51/2019)
AU - Wannasarit, Saowanee
AU - Wang, Shiqi
AU - Figueiredo, Patricia
AU - Trujillo Olvera, Claudia Ximenia
AU - Eburnea, Francesca
AU - Simón-Gracia, Lorena
AU - Correia, Alexandra
AU - Ding, Yaping
AU - Teesalu, Tambet
AU - Liu, Dongfei
AU - Wiwattanapatapee, Ruedeekorn
AU - Santos, Hélder A.
AU - Li, Wei
PY - 2019/12/19
Y1 - 2019/12/19
N2 - Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐co‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
AB - Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐co‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
KW - ADENOVIRUS
KW - CARRIERS
KW - CELL-PENETRATING PEPTIDES
KW - CHALLENGES
KW - DESIGN
KW - DRUG-DELIVERY
KW - EFFICIENT
KW - ENDOSOMAL ESCAPE
KW - INHIBITORS
KW - STRATEGIES
KW - drug delivery
KW - endosomal escape
KW - microfluidics
KW - pH-responsive
KW - polymer nanoparticles
KW - 116 Chemical sciences
KW - 221 Nano-technology
KW - 317 Pharmacy
U2 - 10.1002/adfm.201970351
DO - 10.1002/adfm.201970351
M3 - Other articles
VL - 29
SP - 1970351
JO - Advanced Functional Materials
JF - Advanced Functional Materials
SN - 1616-301X
IS - 51
ER -