Lizhi Zhao

Fabrication of Complex Micelles with Tunable Shell for Application in Controlled Drug Release

At room temperature, diblock copolymers of PLA-b-PNIPAM and PEG-b-PLA self-assembled into complex micelles with a PLA core and a mixed PEG/PNIPAM shell. By increasing the temperature, these complex micelles could be converted into a core-shell-corona structure composed of a PLA core, a collapsed PNIPAM shell and a soluble PEG corona, and the PEG chains stretched from the inner core to outside, leading to the formation of PEG channels. The PEG channels could be used for the exchange of substance between the core and the external environment. Compared with core-shell micelles, complex micelles with a core-shell-corona structure could avoid the burst diffusion in the release of ibuprofen and inhibit the degradation of PLA by lipase to a certain extent.

Facile Strategy for Synthesis of Silica/Polymer Hybrid Hollow Nanoparticles with Channels

The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol-gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.

Aggregation Behavior of the Template-Removed 5,10,15,20-Tetrakis(4-sulfonatophenyl)porphyrin Chiral Array Directed by Poly(ethylene glycol)-block-poly(l-lysine)

Complexation between 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) was performed via electrostatic interaction. Two kinds of primary arrays of TPPS with different supramolecular chirality induced by PLL were obtained in the resultant complex by inverting the mixing procedure of the two components. These arrays could be displaced by poly(sodium-p-styrenesulfonate) (PSS) from the chiral PLL template through competitive electrostatic complexation, and then PSS formed a polyion complex micelle with PEG-b-PLL. The template-removed TPPS arrays preserved their induced chirality and served as primary subunits for the secondary aggregation of TPPS. The morphology of the secondary aggregates was strongly dependent upon the asymmetric primary supramolecular arrangement of TPPS. The rodlike nanostructure that was ∼200 nm in length was composed of the primary arrays that showed opposite exciton chirality between the J- and H-bands. In contrast, the micrometer-sized fibrils observed were composed of the arrays with the same exciton chirality at the J- and H-bands.

Enhancement of the photostability and photoactivity of metallo-meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrins by polymeric micelles.

Metallo-meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrins (metallo-TPPSs), such as ZnTPPS, have been widely used as photosensitizers. However, their vulnerability to photodegradation significantly limits their applications. In this contribution, we demonstrate a method to enhance the photostability of metallo-TPPSs while retaining photoactivity via encapsulation inside cores of complex micelles. Poly(ethylene glycol)-b-poly(4-vinylpyridine) (PEG-b-P4VP) and metallo-TPPSs can form complex micelles in acidic solution through electrostatic interactions and then undergo axial coordination with the pyridine moieties of PEG-b-P4VP when the pH is adjusted to 7.4. In this way, metallo-TPPSs are entrapped in the hydrophobic, compact micellar cores, which effectively prevents photodegradation of the metallo-TPPSs that would otherwise occur in aqueous solution. In addition, the photodebromination of 2,3-dibromo-3-phenylpropionic acid (DPP) sensitized with ZnTPPS has been used as a model reaction to study the photosensitive activity of ZnTPPS entrapped in complex micelles. The entrapped ZnTPPSs exhibit pronounced activity and have much higher efficiency and faster photosensitive reaction rates than free ZnTPPS.

A Valid Way of Quasi-Quantificationally Controlling the Self-Assembly of Block Copolymers in Confined Space

To mimic nanostructures assembled by biomolecules in organic cells and achieve precise self-assembly of block copolymers, a simple but valid way is introduced to quasi-quantificationally control the aggregation numbers (N(agg)) of polymeric micelles. A three-dimensional and closed microconfinement similar to a cell is constructed by W/O inverse emulsion as the spot for self-assembly of the pH-responsive block copolymer poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP). The N(agg) values of the resulting polymeric micelles are effectively controlled by tuning the number of polymer chains encapsulated in isolated water pools. Micelles with different N(agg) values are successfully prepared and characterized by atomic force microscopy, transmission electron microscopy, and dynamic light scattering. When the number of polymer chains enclosed in a water pool (N(chain)) is less than the average N(agg) of normal micelles generated in bulk aqueous solution, the resultant aggregates formed in the confined spaces always have lower N(agg) as well as smaller sizes than the normal micelles do, while normal micelles predominantly form when N(chain) > N(agg) (normal micelle).

Interaction of FeIII-tetra-(4-sulfonatophenyl)-porphyrin with copolymers and aggregation in complex micelles.

Aggregation of Fe(III)-tetra-(4-sulfonatophenyl)-porphyrin (Fe(III)TPPS) was studied in the presence of block copolymers, poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP), poly(ethylene glycol)-block-poly(2-(dimethylamino)ethyl methylacrylate) (PEG-b-PDMAEMA), and poly(ethylene glycol)-block-poly(β-cyclodextrin) (PEG-b-PCD). The interaction between the iron porphyrin and the blocks, P4VP, PDMAEMA, and PCD, led to the formation of copolymers/Fe(III)TPPS complex micelles with a PEG shell and determined the species of Fe(III)TPPS. The electrostatic interaction of protonated P4VP and PDMAEMA with Fe(III)TPPS remarkably decreased the apparent pKd of Fe(III)TPPS and led to a micellar μ-oxo dimer of the iron porphyrin. At pH above the pKa of P4VP, Fe(III)TPPS was kept inside the hydrophobic P4VP core and formed an encapsulated μ-oxo dimer. However, when above the pKa of PDMAEMA, Fe(III)TPPS escaped from the hydrophobic PDMAEMA core, existing as a free μ-oxo dimer. PCD caused the monomer of the porphyrin because of the inclusion complexation between the β-cyclodextrin residues and Fe(III)TPPS. The two micellar monomer species Fe(III)TPPS(H2O)2 and Fe(III)TPPS(OH) were obtained with an equilibrium pKa ~ 6.4.