(711f) Self-Assembled Peptide-Conjugated Polymer Nanoparticles for Tumor Targeting
AIChE Annual Meeting
Friday, November 13, 2009 - 2:20pm to 2:40pm
Short sequences of amino acids are especially attractive for self-assembly because nanostructures with varying size, shape, morphology, and surface functional group can be assembled by arranging the 24 naturally accruing amino acids in different sequences or by changing the sequence length. It has been demonstrated that the peptide CV6K2 spontaneously self-assembles in aqueous environment to form nanospheres (NPs) with relatively uniform size distribution. Poly(lactide fumarate) (PLAF) macromer alone does not produce NPs but blends of PLAF and amphiphilic poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers produce NPs with relatively wide distribution. The objective of this work was to investigate self-assembly and release characteristics of chemotherpauetic drugs from CV6K2-conjugated PLAF nanoparticles. CV6K2 peptides self-assembled into NPs with 70 nm average size and narrow distribution of 30-110 nm. PLAF macromers alone did not produce particles but blends of PLAF and PLEOF macromers produced NPs with 300 nm average size and relatively wide distribution of 160-430 nm. Interestingly, when CV6K2 was conjugated to PLAF and self-assembled in the absence of PLEOF, NPs with 110 nm average size and relatively narrow distribution of 50-170 nm were produced. Furthermore, When a mutant C(V2K)2V2 peptide (a peptide sequence with the same composition as CV6K2 that does not self-assemble into NPs) was conjugated to PLAF, the conjugate self-assembled into NPs with average and distribution similar to PLAF-PLEOF blend. These results demonstrate that the CV6K2 peptide induced self-assembly when conjugated to a non self-assembling PLAF macromer. Furthermoer, the self-assembled CV6K2-PLAF NPs degraded linearly by matrix erosion and released Paclitaxel or Doxorubicin at a constant rate concurrent with matrix erosion. The narrow size distribution peptide conjuagted NPs are potentially attractive for targeted tumor drug delivery.