Functional Biomaterials: Multifunctional Nanoparticles as Controlled Release Platforms

Controlled release technology is indispensible for the repair and regeneration of healthy tissues as well as the treatment of diseases. Uncontrolled presentation of morphogens elicits undesirable inflammatory responses from healthy tissues. Similarly, the burst release of anticancer drugs not only leads to severe toxic effects on the healthy tissues but also induces drug resistance in the target cells. We have created several types of block copolymer nanoparticles containing distinct compartments suitable for the sequestration of hydrophobic, anti–cancer drugs as well as hydrophilic, morphogenic factors.

For example, amphiphilic block copolymers consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(ε–caprolactone) bearing pendent cyclic ketals have been synthesized and characterized. Under appropriate conditions, the copolymer readily assembled into spherical nanoparticles of ~120 nm. A hydrophobic, anticancer drug camptothecin (CPT) was successfully encapsulated in the block copolymer nanoparticles; and its encapsulation efficiency and release kinetics were strongly dependent on the copolymer composition and crystallinity. In vitro cytoxicity assay showed that the blank nanoparticles were not toxic to the cultured bone metastatic prostate cancer cells (C4–2B). Compared to the free drug, the encapsulated CPT was more effective in inducing apoptotic responses in C4–2B cells.

Nanoparticles derived from amphiphilic block copolymers are also attractive vehicles for the delivery and controlled release of morphogenic factors, such as bone morphogenetic protein 2 (BMP–2). We have synthesized amphiphilic diblock copolymers comprised of a hydrophilic, poly(acrylic acid) (PAA) block and a rubbery, hydrophobic poly(n–butyl acrylate) (PnBA) (PAA–b–PnBA) block and multiblock copolymers consisting of a hydrophilic PAA block alternating with glassy, hydrophobic poly(styrene) (PS) segments (PAA–b–PS)n. Both polymers self–assembled into defined micellar structures with an average diameter of 20 and 40 nm, respectively. Partial esterification of the PAA block in both types of copolymers led to the introduction of acrylate groups, through which a heparin–binding peptide was conjugated. BMP–2 was released from these multifunctional nanoparticles in a controlled manner over a prolonged period of time.


  • Ayyappan K. Rajasekaran, Nemours Center for Childhood Cancer Research

Selected Publications:

  1. Krishnan, V.; Xu, X.; Barwe, S. P.; Yang, X.; Czymmek, K.; Waldman, S. A.; Mason, R. W.; Jia, X.; Rajasekaran, A. K.* "Dexamethasone–Loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhances Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine", Mol. Pharm., 2013, 10, 2199–2210.
  2. Wang, X.; Gurski, L. A.; Zhong, S.; Xu, X.; Pochan, D. J; Farach–Carson, M. C.; Jia, X.* "Amphiphilic Block Co–polyesters Bearing Pendant Cyclic Ketal Groups as Nanocarriers for Controlled Release of Camptothecin", J. Biomat. Sci.–Polym. E, 2011, 22, 1275–1298.
  3. Greene, A. C., Xiao, L.; Kiick, K. L.*; Jia, X.* "Multiblock Copolymers of Poly(Acrylic Acid–b–Styrene) as a Drug Delivery Platform", Macromolecules, 2011, 44, 1942–1951.