Tailoring Porphyrin Conjugation for Nanoassembly-Driven Phototheranostic Properties

Abstract

Lipoprotein mimetic nanostructures, which consist of an amphiphilic lipid shell, a hydrophobic core, and an apolipoprotein mimetic peptide, serve as a versatile platform for the design of drug delivery vehicles as well as the investigation of supramolecular assemblies. Porphyrin incorporation into biomimetic lipoproteins allows one to take advantage of the inherent multimodal photophysical properties of porphyrins, yielding various fluorescence, photoacoustic, and photodynamic agents. To facilitate their incorporation into a lipoprotein structure, porphyrins have been conjugated through a variety of strategies. However, the effects of the conjugate structure on the associated nanoparticle’s phototherapeutic properties warrants further investigation. Herein, we systematically investigated the effects of two widely utilized porphyrin conjugates, oleylamide and lipid, on biophotonic properties of their resultant porphyrin-lipoprotein nanoparticles in vitro and in vivo. Specifically, we demonstrated that incorporation of the porphyrin moiety as an oleylamide conjugate leads to a highly stable J-aggregate with strong photoacoustic contrast, while incorporation as an ampiphilic lipid moiety into the lipid shell yields an effective fluorescent and photodynamic agent. The current study proposes a rational design strategy for next-generation lipoprotein-based phototheranostic agents, for which nanoassembly-driven biophotonic and therapeutic properties can be tailored through the specific selection of porphyrin conjugate structures.

Acid‐Activatable Transmorphic Peptide‐Based Nanomaterials for Photodynamic Therapy

“…Thepeptide-porphyrin conjugate was synthesized through solid phase peptide synthesis.InF igure S1, S2, S3 and S4, the MALDI-TOFM S, LC-MS, 1 HNMR and 13 CNMR results indicated high-purity conjugates were obtained after purification by HPLC.Dynamic light scattering (DLS) showed that the PWG molecules self-assembled into PWG nanoparticles with an average diameter of approximately 160 nm (Figure 1a)a nd al ow polydispersity index (PDI) of 0.173 in aqueous solution. Nanoparticles in the sub-200 nm size range have great potential in preferentially accumulating in tumor tissue based on the EPR effect.…”

“…[2b, 12] In addition, peptide-photosensitizer conjugates have been synthesized to create multifunctional nanostructures for PDT. [13] Once released in the tumor site,l ow molecular weight photosensitizers tend to quickly diffuse away and get cleared from tumor tissues,c ausing limited tumor accumulation and short retention times,which strongly limit the application of PDT in clinical trials for cancer therapy. [14] Thus,i ti su rgent to develop nanomaterials to overcome this issue.W ang, Lam and co-workers developed several stimuli-responsive in situ self-assembled and transformable peptide-based nanoparticles which underwent at ransformation to fibrillar structures in the tumor microenvironment;these structures performed excellently in tumor imaging and therapy in vivo by blocking for example HER2 dimerization.…”

In situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy

“…The stability of nanovesicles in a physiological environment with albumin was evaluated by the absorption intensity ratio between J-aggregates (463 nm) of THPG vesicles and the THPG unimers (425 nm) throughout 48 h (n = 3, Supplementary Fig. 15) 24,25 . As a result, the ratio shows only slight change both in PBS and PBS with 10% fetal bovine serum (FBS), which suggests the high optical stability of THPG vesicles in a physiological environment.…”

“…However, up to now, most of the vesicular PTAs are limited to liposomes. The stability of liposomes is not good enough and should be enhanced by the addition of cholesterol or else for further application in PTT 24,25 . Thus, it is highly challenging to develop vesicular PTAs with both stable structure and high photothermal conversion ability.…”

Porphyrin-lipid stabilized paclitaxel nanoemulsion for combined photodynamic therapy and chemotherapy

“…Administration of porphyrin-lipid at doses of 1000 mg/kg elicited minimal acute toxicities in mice [ 28 , 32 ]. We have previously used porphyrin-lipid as a building block to create several multimodal nanoparticle platforms, including liposome-like porphysomes (aqueous-core) [ 28 ], porphyrin nanodroplets (liquefied gas-core) [ 33 ], and ultrasmall porphyrin lipoproteins [ 34 , 35 ]. Herein, we utilized porphyrin-lipid to stabilize water/oil interface to create porphyrin-lipid nanoemulsion with paclitaxel loaded in the oil core (PLNE-PTX).…”