Dendritic Molecular Intracellular Transporters and Methods of Making and Using Same

A method of preparing a compound having the structure:

• wherein n is an integer from 1 to 9,
• wherein R3 is hydrogen or alkyl,
• wherein R4 and R7 are, independently, hydrogen, alkyloxycarbonyl, alkyl, or acyl;
• wherein R7 is hydrogen, alkyl, or acyl;
• wherein Y comprises a nitro group, an amine group, an amide group, azide group, or an alkyloxycarbonyl protected amine group or a derivative thereof,
• the method comprising the steps of:
• a. providing a first compound comprising the structure:
• wherein X comprises OH, halogen, or OC(O)-alkyl;
• b. coupling the first compound with at least about three molar equivalents of a second compound comprising the structure:
• wherein G1 is an ester-protecting group;
• c. removing the ester-protecting group;
• d. reacting the product of step (c) with at least about three molar equivalents of a third compound comprising the structure:
• wherein G2 is an amine-protecting group;
• e. removing the amine-protecting group;
• and
• f. functionalizing the product of step (e) with at least three molar equivalents of a guanidine-providing agent.

An intracellular delivery composition comprising the general structure:

• P-L-B—F,
• wherein P is payload moiety;
• wherein L is a linking moiety comprising the structure:
• wherein o and p are, independently, zero or a positive integer;
• wherein B is a branching moiety comprising the structure:
• and
• wherein F is a functional moiety comprising at least one guanidinium residue.

A method of nanoparticle formation comprising the steps of:

• a. providing a reactor capable of imparting a stimulus and
• b. adding to the reactor a block copolymer comprising at least two reactive residues, thereby imparting the stimulus on at least a portion of the block copolymer;
• wherein the at least two reactive residues form reactive intermediates upon exposure to the stimulus, and
• wherein the reactive intermediates are capable of undergoing a bond-forming reaction.