In this work, synthesis of two cross-linked polymeric systems through isoxazoline ring formation using nitrile oxide-acrylate click chemistry has been described. In the first system, styrenic block copolymer with oxime-functionalized middle block was synthesized using S,S'-bis(α,α'-dimethyl-α″-acetic acid)trithiocarbonate as chain-transfer agent using reversible addition fragmentation chain-transfer technique. This block copolymer was further utilized to prepare core cross-linked star polymers by reacting with a four-arm acrylic cross-linker by employing environment-friendly, nontoxic PhI(OAc)2-mediated "click reaction" via the formation of isoxazoline ring. In the second system, two linear styrenic block copolymers, one containing oxime and another containing acrylate group, were reacted to form a cross-linked (CS) polymeric system. Formation of cross-linked polymers and isoxazoline ring was confirmed by Fourier transform infrared spectroscopy, gel permeation chromatography, NMR spectroscopy, and dynamic light scattering studies. Later, we also demonstrated that in aqueous medium these CS polymers produced polymeric nanoparticles (NPs), which can be used as potential carriers of hydrophobic drug molecules. The loading capacity of the hydrophobic domains has been investigated using coumarin dyes with varying hydrophobicity through steady-state and time-resolved spectroscopy studies. The polymeric NPs were also shown to successfully encapsulate a hydrophobic drug doxorubicin.