Polyelectrolyte nanogels decorated with monoclonal antibody for targeted drug delivery

Abstract

Novel surface-functionalized cross-linked nanogels were developed as a platform to allow conjugation of monoclonal antibodies (mAb) for targeted drug delivery. Well-defined diblock copolymers of poly(ethylene glycol)-b-poly(methacrylic acid) (PEG-b-PMA) with PEG terminal aldehyde functionality were synthesized by atom transfer radical polymerization (ATRP) and characterized by GPC and 1 H NMR. These copolymers were used to prepare nanogels via condensation of PEG-b-PMA with Ca 2+ ions into micelle-like aggregates, cross-linking of the PMA/Ca 2+ cores and removal of Ca 2+ ions. The resulting nanogels represent highly swollen spherical polyelectrolyte particles with free terminal aldehyde functionalities at the nonionic PEG chains. A reductive amination reaction between aldehyde groups and amino groups of mAb resulted in effective conjugation to the nanogels of mAb CC49 against tumor-associated glycoprotein 72 (TAG-72). The mAb retained the binding affinity to bovine submaxillary mucin after conjugation as shown by surface plasmon resonance (SPR). Therefore, aldehyde functionalized nanogels can be linked to mAb using a simple, one-step approach. They may have potential for targeted delivery of diagnostic and therapeutic agents to tumors.

Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer

“…6) compared to PEG-poly(methacrylic acid) (PEG-PMA) cl -micelles containing entirely hydrophilic cross-linked PMA cores [22]. For example, PEG-PMA 133 and PEG-PMA 75 cl -micelles were characterized by dimension aspect ratios of 13.3 and 15.0, respectively.…”

Carborane confined nanoparticles for boron neutron capture therapy: Improved stability, blood circulation time and tumor accumulation

“…[11] Thus, the development of a 10 B-compound confined delivery system, which does not allow leakage of the stabilization of micelles, introducing chemical linkages into either the shell or the core segment to avoid the loss of micelle integrity. [18]- [20] We have also previously reported the preparation of core-polymerized PEG-b-PLA micelles possessing a methacryloyl group at the PLA chain end. Through the radical polymerization, [21], [22] the core-polymerized micelles eventually showed high dispersibility even after lyophilization as well as high stability against dilution, temperature changes and sodium dodecyl sulfate solution.…”

Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1

“…The mAb modified cross-linked nanogels had average diameter of 120-130 nm, low polydispersity indices (PdI50.13) and formed stable aqueous dispersion. These negatively charged nanogels (z-potential ¼ À15 ± 5 mV) were efficiently loaded with cisplatin: loading capacity was 30-35% and entrapment efficiency was $45% (Nukolova et al, 2011b). The drug release from nanogels was sustained, with 16.5 ± 2.1% of release in 24 h, 29.9 ± 2.8% in 3 days and 47.8 ± 3.1% in a week.…”

“…Nanogels were synthesized using a block ionomer complex of the PEG-b-PMAA/Ca2+ as a template (Nukolova et al, 2011b), prepared form aqueous solutions of PEG-b-PMAA and CaCl 2 at a molar ratio of [Ca2+]/[COO] ¼ 1.3. Then chains of the PMAA were cross-linked overnight at room temperature (r.t.) using 1,2-ethylenediamine and…”

“…The amount of attached mAbs was determined by micro bicinchoninic acid (BCA) protein colorimetric assay. Nanogels were loaded with cisplatin ([cisplatin]/ [COOH] ¼ 0.5) as described earlier (Nukolova et al, 2011b). Unbound cisplatin was removed by ultrafiltration using centrifugal filters Amicon YM-30.…”