Shedding light on surface exposition of poly(ethylene glycol) and folate targeting units on nanoparticles of poly(ε-caprolactone) diblock copolymers: Beyond a paradigm

Surface Exposure of PEG and Amines on Biodegradable Nanoparticles as a Strategy to Tune Their Interaction with Protein-Rich Biological Media

“…The black spectrum shows the typical dual band fluorescence spectrum of HSA, which reflects the contribution of the tyrosine (λ em ca 310 nm) and tryptophan (λ em ca 340 nm) fluorogenic centers. This strong emission is quenched upon addition of PEG-PCL NPs simply due to static quenching effects arising by the massive aggregation of HSA on the NPs [3]. This result suggests that: (i) A PEG shell is unable to prevent NP–protein hydrophobic interactions; (ii) Am-NPs adsorb HSA, presumably due to electrostatic interactions, and (iii) amine-PEG NPs interact with HSA through combined hydrophobic/electrostatic interaction.…”

“…Fluorescence spectroscopy was used to assess the ‘quenching’ effect of NPs on the ability of certain residues of the protein to emit light. Following preparation, the samples were incubated at RT for 1 h. Then, the emission spectra were acquired (Ex = 278 nm) (RF-6000, Shimadzu Corporation, Tokyo, Japan) [3]. At different time points (0, 4, and 24 h), size, ζ potential, and scattering were measured as described above.…”

“…On the other hand, the hydrophilic outer shell can be tailored toward deliberate interactions with the biological environment, besides providing superior physical stability to the entire manufacturing process [1,2]. The effects of PEGylation are closely related to the PEG molecular weight, the number of PEG chains located on NP surface, and the corresponding orientation (brush/mushroom), each of which can be affected by the preparation method [3,4].…”

Nanoparticles decorated with folate based on a site-selective αCD-rotaxanated PEG-b-PCL copolymer for targeted cancer therapy

“…In the case of PEG-modified diblock copolymers, the peculiar solubility profile of PEG, which is soluble in both aqueous and organic solvents, can generate NPs where PEG segments are segregated in the lipophilic core and thus not exposed completely on the NP surface. 6,7 Moreover, when lipophilic targeting moieties (e.g., folate) are covalently linked to the -OH end of PEG chains, PEG segregation in the hydrophobic blocks can further increase, thus subtracting targeting elements from the NP surface. 8 In the context of folate-decorated NPs able to deliver a drug cargo to cancer cells overexpressing the folate receptor (FR)α, we tried to tackle this drawback by encouraging folate location on the surface of biodegradable poly(ethylene glycol)-poly(εcaprolactone) (PEG-b-PCL) NPs via non-covalent interactions of folate with the hydroxypropyl derivative of β-cyclodextrins (CDs).…”

Fine tuning neuronal targeting of nanoparticles by adjusting the ligand grafting density and combining PEG spacers of different length

“…To date, few studies have considered in conjugation fundamental aspects for targeted NP design such as the effect of the PEG chain length, flexibility and conformation on ligand-receptor interactions. Both the targeting ligand density and PEG conformation at the NP surface -brush or mushroom-like -should be tightly balanced to achieve NP maximum cell interaction and internalization [10], [16]. In fact, the PEGylation of NPs with identical single chains could hinder the ligand free motion, particularly at high PEG densities, resulting in a reduced accessibility of the ligands towards their cellular receptors [17].…”